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1.
Medicine (Baltimore) ; 100(29): e26491, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398005

RESUMO

ABSTRACT: Hepatocellular carcinoma (HCC) is 1 of the deadliest malignancies worldwide. Despite significant advances in diagnosis and treatment, the mortality rate from HCC persists at a substantial level. Construction of a prognostic model that can reliably predict HCC patients' overall survival is urgently needed.Two RNA-seq dataset (the Cancer Genome Atlas and International Cancer Genome Consortium) and 1 microarray dataset (GSE14520) were included in our study. RNA-binding proteins (RBPs) in HCC patients was examined by differentially expressed genes analysis, functional enrichment analysis and protein-protein interaction network analysis. Subsequently, the Cancer Genome Atlas dataset was randomly divided into training and testing cohort with a prognostic model developed in the training cohort. In order to evaluate the prognostic value of the model, a comprehensive survival assessment was conducted.Five RBPs (ribosomal protein L10-like, enhancer of zeste homolog 2 (EZH2), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A), zinc finger protein 239, interferon-induced protein with tetratricopeptide repeats 1) were used to construct the model. The model accurately predicted the prognosis of liver cancer patients in both the training cohort and validation cohort. HCC patients could be assigned into a high-risk group and a low-risk group by this model, and the overall survival of these 2 groups was significantly different (P  < .05). Furthermore, the risk scores obtained by this model were highly correlated with immune cell infiltration.The prognostic model helps to identify HCC patients at high risk of mortality, which optimizes decision-making for individualized treatment.


Assuntos
Carcinoma Hepatocelular/complicações , Prognóstico , Proteínas com Motivo de Reconhecimento de RNA/análise , Área Sob a Curva , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/mortalidade , Modelos de Riscos Proporcionais , Curva ROC , Medição de Risco/métodos , Medição de Risco/normas , Medição de Risco/estatística & dados numéricos , Análise de Sobrevida
2.
PLoS One ; 16(8): e0256544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34437610

RESUMO

BACKGROUND: Patients with hepatocellular carcinoma (HCC) represent a vulnerable population potentially negatively affected by COVID-19-associated reallocation of healthcare resources. Here, we report the impact of COVID-19 on the management of HCC patients in a large tertiary care hospital. METHODS: We retrospectively analyzed clinical data of HCC patients who presented at the Vienna General Hospital, between 01/DEC/2019 and 30/JUN/2020. We compared patient care before (period 1) and after (period 2) implementation of COVID-19-associated healthcare restrictions on 16/MAR/2020. RESULTS: Of 126 patients, majority was male (n = 104, 83%) with a mean age of 66±11 years. Half of patients (n = 57, 45%) had impaired liver function (Child-Pugh stage B/C) and 91 (72%) had intermediate-advanced stage HCC (BCLC B-D). New treatment, was initiated in 68 (54%) patients. Number of new HCC diagnoses did not differ between the two periods (n = 14 vs. 14). While personal visits were reduced, an increase in teleconsultation was observed (period 2). Number of patients with visit delays (n = 31 (30%) vs. n = 10 (10%); p = 0.001) and imaging delays (n = 25 (25%) vs. n = 7 (7%); p = 0.001) was higher in period 2. Accordingly, a reduced number of patients was discussed in interdisciplinary tumor boards (lowest number in April (n = 24), compared to a median number of 57 patients during period 1). Median number of elective/non-elective admissions was not different between the periods. One patient contracted COVID-19 with lethal outcome. CONCLUSIONS: Changes in patient care included reduced personal contacts but increased telephone visits, and delays in diagnostic procedures. The effects on long-term outcome need to be determined.


Assuntos
COVID-19/epidemiologia , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , COVID-19/virologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Diagnóstico Tardio , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pandemias , Pacientes/psicologia , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Taxa de Sobrevida , Telemedicina , Centros de Atenção Terciária
3.
Medicine (Baltimore) ; 100(33): e27000, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414987

RESUMO

ABSTRACT: Intermediate-stage hepatocellular carcinoma (HCC) is heterogeneous in terms of tumor size, number, and effects on liver function. Various noninvasive models have been proposed to assess functional hepatic reserve or fibrosis severity in patients with HCC. This study assessed the feasibility of 10 noninvasive models and compared their prognostic ability for patients with intermediate-stage HCC.This study retrospectively enrolled 493 patients with intermediate-stage HCC who received treatment at China Medical University Hospital from January 2012 to November 2018. Demographic data, clinical features, and factors associated with overall survival (OS) were recorded at baseline. Receiver-operating characteristic curve analysis and the DeLong method were respectively employed to evaluate and compare the models' OS prediction performance.Of the 493 patients, 373 (75.7%) were male, and 275 (55.8%) had liver cirrhosis (LC). The median age was 64 years (interquartile range: 55-72). Most patients had tumor volume ≤50% (n = 424, 86.0%), and the maximum tumor size was 6.0 (4.0-8.5) cm. The median α-fetoprotein was 36.25 (6.13-552.91) ng/mL. The patients underwent transarterial chemoembolization (TACE, n = 349) or surgery (n = 144). The median follow-up period was 26.07 (9.77-48.27) months. Across the 10 models, the albumin-bilirubin (ALBI) score had the highest area under the receiver operating characteristic curve (AUROC) (0.644, 95% confidence interval: 0.595-0.693) in all patients. In subgroup analyses, the Lok index, platelet-albumin-bilirubin score, ALBI score, and Lok index had the highest AUROC values in patients without cirrhosis, with cirrhosis, undergoing TACE, and undergoing surgery, respectively. Multivariate Cox regression analysis revealed that independent predictors of longer OS were ALBI grade 1 in all patients, patients with LC, and patients undergoing TACE and Lok index grade 1 in patients without LC and patients undergoing surgery.Among the 10 noninvasive models, ALBI score exhibited the highest diagnostic value in predicting OS for all patients, patients with cirrhosis, and those undergoing TACE, and Lok index grade exhibited the highest diagnostic value in predicting OS in patients without cirrhosis and those undergoing surgery.


Assuntos
Carcinoma Hepatocelular/mortalidade , Valor Preditivo dos Testes , Prognóstico , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Taiwan/epidemiologia
4.
Medicine (Baltimore) ; 100(33): e26948, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414957

RESUMO

ABSTRACT: Aberrant immunity has been associated with the initiation and progression of cancers such as hepatocellular carcinoma (HCC). Here, we aim to develop a signature based on immune-related genes (IRGs) to predict the prognosis of HCC patients. The gene expression profiles of 891 HCC samples were derived from 4 publicly accessible datasets. A total of 1534 IRGs from Immunology Database and Analysis Portal website were obtained as candidate genes for prognostic assessment. Using least absolute shrinkage and selection operator (LASSO) regression analysis, 12 IRGs were selected as prognostic biomarkers and were then aggregated to generate an IRG score for each HCC sample. In the training dataset (n = 365), patients with high IRG scores showed a remarkably poorer overall survival than those with low IRG scores (log-rank P < .001). Similar results were documented in 3 independent testing datasets (n = 226, 221, 79, respectively). Multivariate Cox regression and stratified analyses indicated that the IRG score was an independent and robust signature to predict the overall survival in HCC patients. Patients with high IRG scores tended to be in advanced TNM stages, with increased risks of tumor recurrence and metastasis. More importantly, the IRG score was strongly associated with certain immune cell counts, gene expression of immune checkpoints, estimated immune score, and mutation of critical genes in HCC. In conclusion, the proposed IRG score can predict the prognosis and reflect the tumor immune microenvironment of HCC patients, which may facilitate the individualized treatment and provide potential immunotherapeutic targets.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Imunidade/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Transcriptoma , Microambiente Tumoral/imunologia
5.
Bioengineered ; 12(1): 4054-4069, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34369278

RESUMO

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = -0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan-Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , Carcinoma Hepatocelular/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/genética , Receptores Virais/genética , alfa-Fetoproteínas/genética , Fatores Etários , Idoso , Enzima de Conversão de Angiotensina 2/metabolismo , Área Sob a Curva , COVID-19/virologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Bases de Dados Genéticas , Conjuntos de Dados como Assunto , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/classificação , Proteínas de Neoplasias/metabolismo , Fatores de Proteção , Mapeamento de Interação de Proteínas , Curva ROC , Receptores Virais/metabolismo , SARS-CoV-2/patogenicidade , Análise de Sobrevida , alfa-Fetoproteínas/metabolismo
6.
Anticancer Res ; 41(8): 3933-3940, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281856

RESUMO

BACKGROUND: Oligometastatic cancer (OM) is possibly associated with relatively better survival outcomes. We attempted to identify cases in line with this OM concept. PATIENTS AND METHODS: A total of 130 cases with unresectable metastatic pancreatic cancer underwent non-curative surgery from April 2001 to December 2019. Sites of metastasis, clinicopathological information, and surgical outcomes were collected to formulate a better definition of OM. RESULTS: OM criteria were defined as having metastasis to a single organ, few countable lesions and low serum cancer antigen 19-9 level. The median overall survival after non-curative surgery of OM cases was 13.0 months and was significantly better than that of non-OM cases (8.4 months, p=0.003). CONCLUSION: We propose single-organ metastasis of limited tumor volume (H1 or P1/2 by the Japanese Society of Cancer of the Colon and Rectum classification) and low serum cancer antigen 19-9 level (<2,000 U/ml) as new criteria for defining OM pancreatic cancer.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Idoso , Antígeno CA-19-9/sangue , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Masculino , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Neoplasias Peritoneais/sangue , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Carga Tumoral
7.
Lancet Oncol ; 22(7): 977-990, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34143971

RESUMO

BACKGROUND: China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2-3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma. METHODS: This randomised, open-label, phase 2-3 study was done at 50 clinical sites in China. Patients aged 18 years or older with histologically or cytologically diagnosed or clinically confirmed unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. In the phase 2 part of the study, patients received intravenous sintilimab (200 mg every 3 weeks) plus intravenous IBI305 (15 mg/kg every 3 weeks). In the phase 3 part, patients were randomly assigned (2:1) to receive either sintilimab plus IBI305 (sintilimab-bevacizumab biosimilar group) or sorafenib (400 mg orally twice daily; sorafenib group), until disease progression or unacceptable toxicity. Randomisation was done using permuted block randomisation, with a block size of six, via an interactive web response system, and stratified by macrovascular invasion or extrahepatic metastasis, baseline α-fetoprotein, and ECOG performance status. The primary endpoint of the phase 2 part of the study was safety, assessed in all patients who received at least one dose of study drug. The co-primary endpoints of the phase 3 part of the study were overall survival and independent radiological review committee (IRRC)-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03794440. The study is closed to new participants and follow-up is ongoing for long-term outcomes. FINDINGS: Between Feb 11, 2019 and Jan 15, 2020, we enrolled 595 patients: 24 were enrolled directly into the phase 2 safety run-in and 571 were randomly assigned to sintilimab-bevacizumab biosimilar (n=380) or sorafenib (n=191). In the phase 2 part of the trial, 24 patients received at least one dose of the study drug, with an objective response rate of 25·0% (95% CI 9·8-46·7). Based on the preliminary safety and activity data of the phase 2 part, in which grade 3 or worse treatment-related adverse events occurred in seven (29%) of 24 patients, the randomised phase 3 part was started. At data cutoff (Aug 15, 2020), the median follow-up was 10·0 months (IQR 8·5-11·7) in the sintilimab-bevacizumab biosimilar group and 10·0 months (8·4-11·7) in the sorafenib group. Patients in the sintilimab-bevacizumab biosimilar group had a significantly longer IRRC-assessed median progression-free survival (4·6 months [95% CI 4·1-5·7]) than did patients in the sorafenib group (2·8 months [2·7-3·2]; stratified hazard ratio [HR] 0·56, 95% CI 0·46-0·70; p<0·0001). In the first interim analysis of overall survival, sintilimab-bevacizumab biosimilar showed a significantly longer overall survival than did sorafenib (median not reached [95% CI not reached-not reached] vs 10·4 months [8·5-not reached]; HR 0·57, 95% CI 0·43-0·75; p<0·0001). The most common grade 3-4 treatment-emergent adverse events were hypertension (55 [14%] of 380 patients in the sintilimab-bevacizumab biosimilar group vs 11 [6%] of 185 patients in the sorafenib group) and palmar-plantar erythrodysaesthesia syndrome (none vs 22 [12%]). 123 (32%) patients in the sintilimab-bevacizumab biosimilar group and 36 (19%) patients in the sorafenib group had serious adverse events. Treatment-related adverse events that led to death occurred in six (2%) patients in the sintilimab-bevacizumab biosimilar group (one patient with abnormal liver function, one patient with both hepatic failure and gastrointestinal haemorrhage, one patient with interstitial lung disease, one patient with both hepatic faliure and hyperkalemia, one patient with upper gastrointestinal haemorrhage, and one patient with intestinal volvulus) and two (1%) patients in the sorafenib group (one patient with gastrointestinal haemorrhage and one patient with death of unknown cause). INTERPRETATION: Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients. FUNDING: Innovent Biologics. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , China , Progressão da Doença , Feminino , Hepatite B/virologia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Sorafenibe/efeitos adversos , Fatores de Tempo , Adulto Jovem
8.
Medicine (Baltimore) ; 100(24): e26265, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34128857

RESUMO

ABSTRACT: Although evidence for the application of an albumin-bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Here, we enrolled patients who underwent hepatectomy due to single HCC from 2010 to 2014. Analyses were performed to test the potential of the ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.A total of 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤7 cm was remarkably higher than those whose tumors were >7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of OS. The ALBI grade could stratify the patients who had a single tumor ≤7 cm into 2 distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor >7 cm.We showed that the ALBI grading system can predict disease outcomes in patients with a single HCC with a tumor size ≤7 cm. However, the ALBI grade may not predict the prognosis of patients with a single tumor >7 cm.


Assuntos
Bilirrubina/sangue , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Gradação de Tumores/mortalidade , Albumina Sérica/análise , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
9.
Medicine (Baltimore) ; 100(25): e26390, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160420

RESUMO

ABSTRACT: Hepatocellular carcinoma (HCC) involving the inferior vena cava rarely occurs, but its prognosis is extremely poor, with no established treatment to date. This study aimed to analyze the clinical outcome and toxicity of radiotherapy (RT) targeting inferior vena cava tumor thrombus (IVCTT) in HCC patients.From November 2011 to July 2020, medical record of 19 HCC patients who were treated with RT for IVCTT was retrospectively reviewed. RT was delivered using 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and stereotactic body radiation therapy. The median radiation dose was 50 Gy (range, 45-55.8 Gy) for intensity-modulated radiation therapy and three-dimensional conformal radiotherapy. Stereotactic body radiation therapy was performed in 5 patients, for a total of 32 Gy in 4 fractions.The median follow-up duration was 8.1 months (range, 3.3-26.5 months). The median overall survival was 9.4 months (range, 3.7-26.5 months), and the 1-year overall survival rate was 37.1%. Eight of 19 patients (42.1%) had extrahepatic metastasis at the start of RT. Six of 11 patients (54.5%) who did not have extrahepatic metastasis at the start of RT showed extrahepatic metastasis after RT. The major cause of death was progression of extrahepatic metastasis (11 patients, 57.9%). The overall response rate of IVCTT for RT was 84.2%, and the local control rate at the time of the last follow-up was 89.4%. After RT, the most common first progression site was the lungs (9 patients, 47.4%). Most toxicities were grade 1 to 2 gastrointestinal (26.3%) and liver enzyme elevation (68.4%). Three patients occurred pulmonary embolism after RT later than 5 months after.RT is a feasible and safe local therapy for IVCTT, with favorable tumor control and acceptable toxicity. Extrahepatic metastasis is the major progression pattern and a leading cause of death in patients treated with RT. The combination of effective systemic therapy with RT may have to be considered.


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Veia Cava Inferior/patologia , Trombose Venosa/radioterapia , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Progressão da Doença , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Prognóstico , Intervalo Livre de Progressão , Radiocirurgia/efeitos adversos , Dosagem Radioterapêutica , Radioterapia Conformacional/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Veia Cava Inferior/diagnóstico por imagem , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia , Trombose Venosa/patologia
10.
Medicine (Baltimore) ; 100(25): e26506, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160470

RESUMO

ABSTRACT: Many clinical studies have demonstrated that the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and Onodera's prognostic nutritional index (OPNI) are visibly involved in the prognosis of a variety of tumors. In our research, we aim to determin the prognostic impact of NLR, PLR, and OPNI for hepatocellular carcinoma (HCC).Data of hepatocellular carcinoma patients undergoing treatment in Changzhi People's Hospital between 2011 and 2017 were reviewed. 270 patients with HCC were under inclusion criteria. The optimal cut-off points of OPNI, NLR and PLR were determined by using the X-tile program. The overall survival (OS) was analyzed by Kaplan-Meier method. Multivariate analysis was performed using Cox Proportional Hazard Regression model to determine independent prognostic indicators for HCC.As revealed by Univariate and multivariate analysis, OPNI, Treatment, PLR, and BCLC Stage can be used as independent prognostic indicators for HCC. Comparing the P values and hazard ratios, we found out that the OPNI has greatest influence on prognosis in these indexes. The appropriate cut-off points of NLR, PLR, and OPNI were 2.5, 133.3, and 39.5, respectively. High score OPNI group had a better OS. In the analysis between OPNI and clinicopathological characteristics, there were differences in treatment, postoperative therapy, AST, ALBI grade, NLR and PLR between the high OPNI group and the low OPNI group, while others did not.OPNI is a straightforward and effective independent prognostic indicator for HCC.


Assuntos
Plaquetas/imunologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Linfócitos/imunologia , Neutrófilos/imunologia , Avaliação Nutricional , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Quimioterapia Adjuvante , Feminino , Hepatectomia , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Estimativa de Kaplan-Meier , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/terapia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Valores de Referência , Estudos Retrospectivos
11.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072570

RESUMO

Sorafenib, a multi-kinase inhibitor, is the first-line treatment for advanced hepatocellular carcinoma (HCC) patients. However, this drug only provides a short improvement of patients' overall survival, and drug resistance is commonly developed. Thus, the identification of resistant factor(s) or biomarker(s) is needed to develop more efficient therapeutic strategies. Long, non-coding RNAs (lncRNAs) have recently been viewed as attractive cancer biomarkers and drive many important cancer phenotypes. A lncRNA, ZFAS1 (ZNFX1 antisense RNA 1) has been found to promote HCC metastasis. This study found that sorafenib induced ZFAS1 expression specifically in sorafenib-resistant HCC cells. Although ZFAS1 knockdown did not restore the sensitivity of HCC cells to sorafenib, its expression may act as a resistant biomarker for sorafenib therapy. Bioinformatics analysis predicted that sorafenib tended to induce pathways related to endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in sorafenib-resistant HCC cells. In vitro experimental evidence suggested that sorafenib induced protein kinase RNA-like ER kinase (PERK)/activating transcription factor 4 (ATF4)-dependent ZFAS1 expression, and sorafenib resistance could be overcome by PERK/ATF inhibitors. Therefore, PERK/ATF4/ZFAS1 signaling axis might be an attractive therapeutic and prognostic biomarker for sorafenib therapy in HCC.


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Inibidores de Proteínas Quinases/farmacologia , RNA Longo não Codificante/genética , Sorafenibe/farmacologia , eIF-2 Quinase/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Prognóstico , Análise de Sequência de RNA
12.
J Surg Oncol ; 124(4): 598-606, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34061356

RESUMO

BACKGROUND: Phosphorylated mammalian target of rapamycin (p-mTOR) plays a crucial role in the process of cancer progression. Common gene mutations of colorectal cancer lead to the activation of the PI3k/Akt/mTOR pathway. In this study, we determined whether p-mTOR expression in colorectal liver metastases is a predictive marker of prognosis following liver resection. METHODS: Eighty-one patients with colorectal liver metastases who had undergone curative resection were evaluated using immunohistochemistry of p-mTOR. Data regarding clinicopathological features and patient survival were analyzed. RESULTS: The p-mTOR expression in colorectal liver metastases was detected in 55 (67.9%) patients. Patients whose metastases had high p-mTOR expression showed a significantly lower overall survival rate after resection as compared to patients with low p-mTOR expression (p = 0.016), while there was no significant difference in the disease-free survival between the two groups. Repeat resection for recurrence was performed more frequently in patients with p-mTOR positive than others (p = 0.024). Multivariate analysis showed that p-mTOR expression was an independent prognostic factor of overall survival after liver resection (p = 0.019). CONCLUSIONS: mTOR was frequently activated in colorectal liver metastases, and the p-mTOR expression was a biological marker for predicting the overall survival of patients with colorectal liver metastases following liver resection.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/mortalidade , Regulação Neoplásica da Expressão Gênica , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Serina-Treonina Quinases TOR/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Fosforilação , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Serina-Treonina Quinases TOR/genética
13.
Am J Gastroenterol ; 116(9): 1913-1923, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33989225

RESUMO

INTRODUCTION: Patients with cirrhosis and men have been under-represented in most studies examining the clinical benefit of response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC). The aim of this study was to study the association of UDCA response and liver-related death or transplantation, hepatic decompensation, and hepatocellular carcinoma (HCC) in patients with PBC cirrhosis. METHODS: We conducted a retrospective cohort study of veterans, predominantly men, with PBC and compensated cirrhosis to assess the association of UDCA response with the development of all-cause and liver-related mortality or transplantation, hepatic decompensation, and HCC using competing risk time-updating Cox proportional hazards models. RESULTS: We identified 501 subjects with PBC and compensated cirrhosis, including 287 UDCA responders (1,692.8 patient-years [PY] of follow-up) and 214 partial responders (838.9 PY of follow-up). The unadjusted rates of hepatic decompensation (3.8 vs 7.9 per 100 PY, P < 0.0001) and liver-related death or transplantation (3.7 vs 6.2 per 100 PY, P < 0.0001) were lower in UDCA responders compared with partial responders. UDCA response was associated with a lower risk of hepatic decompensation (subhazard ratio [sHR] 0.54, 95% confidence interval [CI] 0.31-0.95, P = 0.03), death from any cause or transplantation (adjusted hazard ratio 0.49, 95% CI 0.33-0.72, P = 0.0002), and liver-related death or transplantation (sHR 0.40, 95% CI 0.24-0.67, P = 0.0004), but not HCC (sHR 0.39, 95% CI 0.60-2.55, P = 0.32). In a sensitivity analysis, the presence of portal hypertension was associated with the highest UDCA-associated effect. DISCUSSION: UDCA response is associated with a reduction in decompensation, all-cause, and liver-related death or transplantation in a cohort of predominantly male patients with cirrhosis, with the highest benefit in patients with portal hypertension.


Assuntos
Carcinoma Hepatocelular/mortalidade , Colagogos e Coleréticos/uso terapêutico , Cirrose Hepática Biliar/mortalidade , Neoplasias Hepáticas/mortalidade , Transplante de Fígado , Ácido Ursodesoxicólico/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/tratamento farmacológico , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
14.
APMIS ; 129(8): 470-479, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33950532

RESUMO

Toll-like receptors (TLRs) are components of innate immunity, but also have a role in carcinogenesis. The prognostic value of TLR5 and TLR8 tumor expression was examined in contrast with known risk markers Ki67 and p53. All HCC patients from Oulu University Hospital with available representative tumor sample were included in this study (n = 182). TLR5, TLR8, Ki67, and p53 expression were investigated by immunohistochemistry. The relation between patient survival and TLR, Ki67, and p53 expression was calculated with Cox regression adjusted for confounding factors. TLR5 cytoplasm intensity was associated with 5-year overall (strong 0.0% vs weak 23.4%, p < 0.001) and disease-specific (strong 0.0% vs weak 34.9%, p < 0.001) survival. TLR5 nuclei percentage was associated with poor 5-year disease-specific survival (high 16.3% vs low 31.5%, p = 0.022). In adjusted analysis, strong TLR5 cytoplasm intensity was an independent risk factor for poor 5-year overall (adjusted HR 1.88, 95% CI 1.26-2.81) and disease-specific (adjusted HR 2.00, 95% CI 1.27-3.15) survival. High Ki67 and p53 expression associated with 5-year overall- and disease-specific survival. TLR8 was not associated with patient survival. This study suggests that TLR5 expression is independently prognostic in HCC with similar point estimate as previously known p53.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Receptor 5 Toll-Like/genética , Receptor 8 Toll-Like/metabolismo , Idoso , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Receptor 5 Toll-Like/metabolismo , Receptor 8 Toll-Like/genética
15.
J Surg Oncol ; 124(3): 334-342, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33961716

RESUMO

BACKGROUND: The relationship between hospital Magnet status recognition and postoperative outcomes following complex cancer surgery remains ill-defined. We sought to characterize Textbook Outcome (TO) rates among patients undergoing (HP) surgery for cancer in Magnet versus non-Magnet centers. METHODS: Medicare beneficiaries undergoing HP surgery between 2015 and 2017 were identified. The association of postoperative TO (no complications/extended length-of-stay/90-day mortality/90-day readmission) with Magnet designation was examined after adjusting for competing risk factors. RESULTS: Among 10,997 patients, 21.3% (n = 2337) patients underwent surgery at Magnet hospitals (non-Magnet centers: 78.7%, n = 8660). On multivariable analysis, patients undergoing HP surgery had comparable odds of achieving a TO at Magnet versus non-Magnet hospitals (hepatectomy: odds ratio [OR]: 1.05, 95% confidence interval [CI]: 0.94-1.17; pancreatectomy-OR: 0.88, 95% CI: 0.74-1.06). Patients treated at hospitals with a high nurse-to-bed ratio had higher odds of achieving a TO irrespective of whether they received surgery at Magnet (high vs. low nurse-to-bed ratio; OR: 1.38; 95% CI: 1.01-1.89) or non-Magnet centers (OR: 1.26; 95% CI: 1.10-1.45). Similarly, hospital HP volume was strongly associated with higher odds of TO following HP surgery in both Magnet (Leapfrog compliant vs. noncompliant; OR: 1.24, 95% CI: 1.06-1.44) and non-Magnet centers (OR: 1.18; 95% CI: 1.11-1.26). CONCLUSION: Hospital Magnet designation was not an independent factor of superior outcomes after HP surgery. Rather, hospital-level factors such as nurse-to-bed ratio and HP procedural volume drove outcomes.


Assuntos
Hospitais/normas , Neoplasias Hepáticas/cirurgia , Medicare/estatística & dados numéricos , Neoplasias Pancreáticas/cirurgia , Idoso , Feminino , Hepatectomia/normas , Hepatectomia/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Análise Multivariada , Pancreatectomia/normas , Pancreatectomia/estatística & dados numéricos , Neoplasias Pancreáticas/mortalidade , Qualidade da Assistência à Saúde , Resultado do Tratamento , Estados Unidos/epidemiologia
16.
BMC Cancer ; 21(1): 490, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941104

RESUMO

BACKGROUND: A prognostic benefit of additive chemotherapy in patients following resection of metachronous colorectal liver metastases (CRLM) remains controversial. Therefore, the goal of this retrospective study was to investigate the impact of perioperative chemotherapy on disease-free survival (DFS) and overall survival (OS) of patients after curative resection of metachronous CRLM. METHODS: In a retrospective single-centre study, patients after curative resection of metachronous CRLM were included and analysed for DFS and OS with regard to the administration of additive chemotherapy. The Kaplan-Meier method was applied to compare DFS and OS while Cox regression models were used to identify independent prognostic variables. RESULTS: Thirty-four of 75 patients were treated with additive 5-FU based chemotherapy. OS was significantly prolonged in this patient subgroup (62 vs 57 months; p = 0.032). Additive chemotherapy significantly improved 10-year survival rates (42% vs 0%, p = 0.023), but not 5-year survival (58% vs 42%, p = 0.24). Multivariate analysis identified additive chemotherapy (p = 0.016, HR 0.44, 95% CI 0.23-0.86), more than five CRLM (p = 0.026, HR 2.46, 95% CI 1.16-10.32) and disease recurrence (0.009, HR 2.70, 95% CI 1.29-5.65) as independent risk factors for OS. CONCLUSION: Additive chemotherapy significantly prolonged OS and 10-year survival in patients after curative resection of metachronous CRLM. Randomized clinical trials are needed in the future to identify optimal chemotherapy regimens for those patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Retais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Capecitabina/administração & dosagem , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
17.
Am J Clin Oncol ; 44(8): 419-422, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34028371

RESUMO

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is a malignant vascular neoplasm representing ∼1% of sarcomas. Due to its rarity, its clinical course is not well characterized and optimal treatment remains unknown. MATERIALS AND METHODS: This was a retrospective review of patients with EHE treated at Stanford University between 1998 and 2020. Demographic characteristics, pathology results, treatment modalities, and clinical outcomes were collected from the electronic medical records. RESULTS: A total of 58 patients had a mean age of 50.6 years and a slight female predominance (52%). Primary disease sites were liver (33%), soft tissue (29%), lung (14%), bone (9%), and mediastinum (9%). A majority (55%) had advanced or metastatic disease. Median overall survival (OS) was 16.9 years, with OS 89% at 1 year, 68% at 5 years, and 64% at 10 years. The longest median OS was associated with soft tissue sites and shortest with lung and mediastinal disease (P=0.03). The localized disease had improved median OS compared with metastatic disease (P=0.02). There was no OS difference between tumors >3 cm and those equal or smaller (P=0.85). Surgery was a common treatment (71%), while radiation and ablation were sometimes used (28% and 9%, respectively). The median time to initiating therapy of any kind was 68 days. The median time to systemic therapy was 114 days. CONCLUSIONS: We report on the clinical characteristics and outcomes of patients with EHE at a large academic center. Treatment options included surgical excision, liver transplant, ablation, radiation, and systemic therapy. A subset of patients had indolent disease not requiring treatment upfront.


Assuntos
Hemangioendotelioma Epitelioide/mortalidade , Hemangioendotelioma Epitelioide/terapia , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Feminino , Hemangioendotelioma Epitelioide/patologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Transplante de Fígado , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/terapia , Resultado do Tratamento
18.
Lancet Oncol ; 22(7): 991-1001, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34051880

RESUMO

BACKGROUND: Understanding patients' experience of cancer treatment is important. We aimed to evaluate patient-reported outcomes (PROs) with atezolizumab plus bevacizumab versus sorafenib in patients with advanced hepatocellular carcinoma in the IMbrave150 trial, which has already shown significant overall survival and progression-free survival benefits with this combination therapy. METHODS: We did an open-label, randomised, phase 3 trial in 111 hospitals and cancer centres across 17 countries or regions. We included patients aged 18 years or older with systemic, treatment-naive, histologically, cytologically, or clinically confirmed unresectable hepatocellular carcinoma and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with disease that was not amenable to curative surgical or locoregional therapies, or progressive disease after surgical or locoregional therapies. Participants were randomly assigned (2:1; using permuted block randomisation [blocks of six], stratified by geographical region; macrovascular invasion, extrahepatic spread, or both; baseline alpha-fetoprotein concentration; and ECOG performance status) to receive 1200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously once every 3 weeks or 400 mg sorafenib orally twice a day, until loss of clinical benefit or unacceptable toxicity. The independent review facility for tumour assessment was masked to the treatment allocation. Previously reported coprimary endpoints were overall survival and independently assessed progression-free survival per Response Evaluation Criteria in Solid Tumors 1.1. Prespecified secondary and exploratory analyses descriptively evaluated treatment effects on patient-reported quality of life, functioning, and disease symptoms per the European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire for cancer (QLQ-C30) and quality-of-life questionnaire for hepatocellular carcinoma (QLQ-HCC18). Time to confirmed deterioration of PROs was analysed in the intention-to-treat population; all other analyses were done in the PRO-evaluable population (patients who had a baseline PRO assessment and at least one assessment after baseline). The trial is ongoing; enrolment is closed. This trial is registered with ClinicalTrials.gov, NCT03434379. FINDINGS: Between March 15, 2018, and Jan 30, 2019, 725 patients were screened and 501 patients were enrolled and randomly assigned to atezolizumab plus bevacizumab (n=336) or sorafenib (n=165). 309 patients in the atezolizumab plus bevacizumab group and 145 patients in the sorafenib group were included in the PRO-evaluable population. At data cutoff (Aug 29, 2019) the median follow-up was 8·6 months (IQR 6·2-10·8). EORTC QLQ-C30 completion rates were 90% or greater for 23 of 24 treatment cycles in both groups (range 88-100% in the atezolizumab plus bevacizumab group and 80-100% in the sorafenib group). EORTC QLQ-HCC18 completion rates were 90% or greater for 20 of 24 cycles in the atezolizumab plus bevacizumab group (range 88-100%) and 21 of 24 cycles in the sorafenib group (range 89-100%). Compared with sorafenib, atezolizumab plus bevacizumab reduced the risk of deterioration on all EORTC QLQ-C30 generic cancer symptom scales that were prespecified for analysis (appetite loss [hazard ratio (HR) 0·57, 95% CI 0·40-0·81], diarrhoea [0·23, 0·16-0·34], fatigue [0·61, 0·46-0·81], pain [0·46, 0·34-0·62]), and two of three EORTC QLQ-HCC18 disease-specific symptom scales that were prespecified for analysis (fatigue [0·60, 0·45-0·80] and pain [0·65, 0·46-0·92], but not jaundice [0·76, 0·55-1·07]). At day 1 of treatment cycle five (after which attrition in the sorafenib group was more than 50%), the mean EORTC QLQ-C30 score changes from baseline in the atezolizumab plus bevacizumab versus sorafenib groups were: -3·29 (SD 17·56) versus -5·83 (20·63) for quality of life, -4·02 (19·42) versus -9·76 (21·33) for role functioning, and -3·77 (12·82) versus -7·60 (15·54) for physical functioning. INTERPRETATION: Prespecified analyses of PRO data showed clinically meaningful benefits in terms of patient-reported quality of life, functioning, and disease symptoms with atezolizumab plus bevacizumab compared with sorafenib, strengthening the combination therapy's positive benefit-risk profile versus that of sorafenib in patients with unresectable hepatocellular carcinoma. FUNDING: F Hoffmann-La Roche and Genentech.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Inibidores de Proteínas Quinases/uso terapêutico , Sorafenibe/uso terapêutico , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Qualidade de Vida , Sorafenibe/efeitos adversos , Fatores de Tempo
19.
Aging (Albany NY) ; 13(9): 12865-12895, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33946043

RESUMO

Hepatitis C virus-associated HCC (HCV-HCC) is a prevalent malignancy worldwide and the molecular mechanisms are still elusive. Here, we screened 240 differentially expressed genes (DEGs) of HCV-HCC from Gene expression omnibus (GEO) and the Cancer Genome Atlas (TCGA), followed by weighted gene coexpression network analysis (WGCNA) to identify the most significant module correlated with the overall survival. 10 hub genes (CCNB1, AURKA, TOP2A, NEK2, CENPF, NUF2, CDKN3, PRC1, ASPM, RACGAP1) were identified by four approaches (Protein-protein interaction networks of the DEGs and of the significant module by WGCNA, and diagnostic and prognostic values), and their abnormal expressions, diagnostic values, and prognostic values were successfully verified. A four hub gene-based prognostic signature was built using the least absolute shrinkage and selection operator (LASSO) algorithm and a multivariate Cox regression model with the ICGC-LIRI-JP cohort (N =112). Kaplan-Meier survival plots (P = 0.0003) and Receiver Operating Characteristic curves (ROC = 0.778) demonstrated the excellent predictive potential for the prognosis of HCV-HCC. Additionally, upstream regulators including transcription factors and miRNAs of hub genes were predicted, and candidate drugs or herbs were identified. These findings provide a firm basis for the exploration of the molecular mechanism and further clinical biomarkers development of HCV-HCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Hepatite C Crônica/patologia , Neoplasias Hepáticas/diagnóstico , RNA Mensageiro/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Biologia Computacional , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Fígado/virologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , MicroRNAs/metabolismo , Valor Preditivo dos Testes , Prognóstico , Mapas de Interação de Proteínas/genética , RNA Mensageiro/genética , Medição de Risco/métodos , Fatores de Transcrição/metabolismo , Transcriptoma/genética
20.
Aging (Albany NY) ; 13(9): 12929-12954, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952716

RESUMO

Liver hepatocellular carcinoma (LIHC) remains one of the most common causes of cancer death. Prior research suggested that the PPM1G gene is involved in LIHC. To explore the role of PPM1G in LIHC, we used several online databases. Expression profiling was performed via the Gene Expression Profiling Interactive Analysis (GEPIA), Hepatocellular Carcinoma Database (HCCDB), Oncomine and Human Protein Atlas (HPA) platforms. Mutation profiles were investigated via cBio Cancer Genomics Portal (cBioPortal). Survival analysis was performed via the Kaplan-Meier (KM) plotter and International Cancer Genome Consortium (ICGC) platforms. The biological function of PPM1G was analyzed via the Enrichr database. The influence of PPM1G expression in the tumor immune microenvironment was assessed via Tumor Immune Estimation Resource (TIMER). PPM1G expression was upregulated in various tumors, including LIHC. Overexpression of PPM1G was associated with poor prognosis in LIHC. PPM1G expression might be regulated by promoter methylation, copy number variations (CNVs) and kinases and correlate with immune infiltration. The gene ontology (GO) terms associated with high PPM1G expression were mRNA splicing and the cell cycle. The results suggest that PPM1G is correlated with the prognosis of LIHC patients and associated with the tumor immune microenvironment in LIHC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Proteína Fosfatase 2C/genética , Microambiente Tumoral/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Variações do Número de Cópias de DNA , Metilação de DNA , Análise Mutacional de DNA , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/imunologia , Redes Reguladoras de Genes/imunologia , Humanos , Estimativa de Kaplan-Meier , Fígado/imunologia , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Mutação , Prognóstico , Regiões Promotoras Genéticas/genética , Microambiente Tumoral/genética , Regulação para Cima/imunologia
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