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1.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5300-5303, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019180

RESUMO

Compared to European-Americans (EAs), the incidence of hepatocellular carcinoma (HCC) is higher in African-Americans (AAs) and is associated with more advanced tumor stage at diagnosis and lower survival rates. The increasing burden makes discovery of novel diagnostic, prognostic, and therapeutic biomarkers distinguishing HCC from underlying cirrhosis a significant focus. In this study, we analyzed tissue and serum samples from 40 HCC cases and 25 patients with liver cirrhosis to identify candidate biomarkers that distinguish HCC from cirrhotic patients in a race specific manner. Through integrative analysis of transcriptomic and metabolomic data, we investigated candidate metabolite biomarkers that are specific to AAs and EAs. The results from this demonstrate the utility of integrating transcriptomic and metabolomic data to prioritize clinically and biologically relevant metabolite biomarkers that can increase understanding of molecular mechanisms driving HCC in different racial groups.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Humanos , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Metabolômica
2.
Medicine (Baltimore) ; 99(40): e22242, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019399

RESUMO

BACKGROUND: To evaluate the clinical value of circulating tumor cell (CTC) detection in peripheral blood for the diagnosis and prognosis of hepatocellular carcinoma (HCC). METHODS: Public databases were searched, and a meta-analysis was performed to determine the specificity, sensitivity, negative- likelihood ratio (NLR) and positive-likelihood ratio (PLR), and diagnostic odds ratio (dOR) of CTC detection for the diagnosis of HCC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed for the association of CTC detection with overall survival (OS) and HCC recurrence. The Meta-DiSc 1.4 and Review Manager 5.2 software programs were used for statistical analysis. RESULTS: Meta-analysis of 20 studies including 1191 patients showed that the specificity, sensitivity, NLR, PLR, and dOR of CTC testing for HCC diagnosis were 0.60 (95% CI = 0.57-0.63), 0.95 (95%CI = 0.93-0.96), 0.36 (95%CI = 0.28-0.48), 11.64 (95%CI = 5.85-23.14), and 38.94 (95%CI = 18.33-82.75), respectively. Meta-analysis of 18 studies including 1466 patients indicated that the OS of CTC-positive HCC patients was less than that of CTC-negative patients (HR = 2.31; 95% CI = 1.55-3.42; P < .01). Meta-analysis of 5 studies including 339 patients revealed that the presence of CTCs in peripheral blood significantly increased the risk of HCC recurrence (HR = 3.03, 95% CI = 1.89-4.86; P < .01). CONCLUSION: CTCs in peripheral blood may be a useful marker for HCC diagnosis. In addition, the prognosis of CTC-positive HCC patients was significantly worse than that of CTC-negative HCC patients. Therefore, further studies are warranted to confirm the clinical potential of CTC detection in peripheral blood in patients with primary HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Células Neoplásicas Circulantes/metabolismo , Biomarcadores Tumorais , Carcinoma Hepatocelular/sangue , Contagem de Células , Humanos , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia , Células Neoplásicas Circulantes/patologia , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Sensibilidade e Especificidade , Análise de Sobrevida
3.
Nat Commun ; 11(1): 4489, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895384

RESUMO

We report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific extracellular vesicle (EV) purification system for early detection of HCC by performing digital scoring on the purified EVs. Earlier detection of HCC creates more opportunities for curative therapeutic interventions. EVs are present in circulation at relatively early stages of disease, providing potential opportunities for HCC early detection. We develop an HCC EV purification system (i.e., EV Click Chips) by synergistically integrating covalent chemistry-mediated EV capture/release, multimarker antibody cocktails, nanostructured substrates, and microfluidic chaotic mixers. We then explore the translational potential of EV Click Chips using 158 plasma samples of HCC patients and control cohorts. The purified HCC EVs are subjected to reverse-transcription droplet digital PCR for quantification of 10 HCC-specific mRNA markers and computation of digital scoring. The HCC EV-derived molecular signatures exhibit great potential for noninvasive early detection of HCC from at-risk cirrhotic patients with an area under receiver operator characteristic curve of 0.93 (95% CI, 0.86 to 1.00; sensitivity = 94.4%, specificity = 88.5%).


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer/métodos , Vesículas Extracelulares/genética , Neoplasias Hepáticas/diagnóstico , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Química Click/instrumentação , Química Click/métodos , Química Computacional , Simulação por Computador , Diagnóstico Diferencial , Dimetilpolisiloxanos/química , Progressão da Doença , Detecção Precoce de Câncer/instrumentação , Feminino , Células Hep G2 , Humanos , Dispositivos Lab-On-A-Chip , Biópsia Líquida/instrumentação , Biópsia Líquida/métodos , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Pessoa de Meia-Idade , Nanoestruturas/química , Nanofios/química , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa/instrumentação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
4.
Anticancer Res ; 40(9): 5271-5276, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878816

RESUMO

BACKGROUND/AIM: Hepatic encephalopathy is an adverse event resulting from lenvatinib use in patients with hepatocellular carcinoma (HCC). We analyzed the influence of lenvatinib on portal venous flow velocity (PVV) and serum ammonia concentration. PATIENTS AND METHODS: Eleven patients with unresectable HCC were enrolled, including three with modified albumin-bilirubin (mALBI) grade 1, three with grade 2a, and five with grade 2b. PVV was measured by Doppler ultrasound sonography before and on day 2 of administration. RESULTS: Out of 11 patients, one developed hepatic encephalopathy. PVV was reduced in 10 patients, and the change from baseline was significantly correlated with lenvatinib dosage. The increase in serum ammonia concentration was affected by lenvatinib dose and baseline hepatic function as a threshold between mALBI grade 2a and 2b statistically. There was no correlation between changes in PVV and serum ammonia concentration. CONCLUSION: Lenvatinib might directly disturb hepatocyte metabolism to result in increased serum ammonia concentration.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Hiperamonemia/etiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Bilirrubina/sangue , Carcinoma Hepatocelular/diagnóstico , Suscetibilidade a Doenças , Feminino , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Humanos , Hiperamonemia/diagnóstico , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Veia Porta/fisiopatologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Fatores de Risco
5.
Medicine (Baltimore) ; 99(34): e21887, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846849

RESUMO

INTRODUCTION: The incidence of hepatocellular carcinoma (HCC) ranks sixth in the world, but its mortality is the third highest due to the lack of early diagnostic markers. Nowadays, the increase of autoantibody levels has been found in many cancers, and many studies have begun to pay attention to the detection of anti-p53 antibodies in HCC. The purpose of this study is to quantitatively and comprehensively analyze the potential diagnostic value of anti-p53 autoantibodies in HCC METHODS:: English articles up to November 2019 were collected. The overall sensitivity and specificity were calculated. Besides, the positive likelihood ratio, negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curves of the overall diagnostic accuracy of anti-p53 antibody were calculated by STATA software. Finally, according to the heterogeneity of the results, the subgroup analysis, and the publication bias were performed. RESULTS: A total of 16 eligible studies were incorporated into this meta-analysis, including 1323 patients with HCC and 1896 control. The pooled sensitivity was 0.28(0.17-0.41) and specificity was 0.98 (0.95-0.99). The pooled DOR was 10.44 (6.31-17.29) and the pooled NLR was 0.74 (0.63-0.86). The area under ROC curve of symmetrical ROC was 0.840. CONCLUSIONS: The anti-p53 antibody has a high specificity for HCC, but the low sensitivity is not perfect and would limit the clinical application. The anti-p53 antibody would help rule out HCC but not help rule in HCC for early diagnosis. Whether combined as a diagnostic panel with other biomarkers or laboratory tests may prove useful requires further study.


Assuntos
Anticorpos/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Estudos de Casos e Controles , Estudos de Avaliação como Assunto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Proteína Supressora de Tumor p53/antagonistas & inibidores
6.
Medicine (Baltimore) ; 99(32): e21702, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769939

RESUMO

Hepatocellular carcinoma (HCC) is a malignant tumor with unsatisfactory prognosis. The abnormal genes expression is significantly associated with initiation and poor prognosis of HCC. The aim of the present study was to identify molecular biomarkers related to the initiation and development of HCC via bioinformatics analysis, so as to provide a certain molecular mechanism for individualized treatment of hepatocellular carcinoma.Three datasets (GSE101685, GSE112790, and GSE121248) from the GEO database were used for the bioinformatics analysis. Differentially expressed genes (DEGs) of HCC and normal liver samples were obtained using GEO2R online tools. Gene ontology term and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were conducted via the Database for Annotation, Visualization, and Integrated Discovery online bioinformatics tool. The protein-protein interaction (PPI) network was constructed by the Search Tool for the Retrieval of Interacting Genes database and hub genes were visualized by Cytoscape. Survival analysis and RNA sequencing expression were conducted by UALCAN and Gene Expression Profiling Interactive Analysis.A total of 115 shared DEGs were identified, including 30 upregulated genes and 85 downregulated genes in HCC samples. P53 signaling pathway and cell cycle were the major enriched pathways for the upregulated DEGs whereas metabolism-related pathways were the major enriched pathways for the downregulated DEGs. The PPI network was established with 105 nodes and 249 edges and 3 significant modules were identified via molecular complex detection. Additionally, 17 candidate genes from these 3 modules were significantly correlated with HCC patient survival and 15 of 17 genes exhibited high expression level in HCC samples. Moreover, 4 hub genes (CCNB1, CDK1, RRM2, BUB1B) were identified for further reanalysis of KEGG pathway, and enriched in 2 pathways, the P53 signaling pathway and cell cycle pathway.Overexpression of CCNB1, CDK1, RRM2, and BUB1B in HCC samples was correlated with poor survival in HCC patients, which could be potential therapeutic targets for HCC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/diagnóstico , Biologia Computacional/estatística & dados numéricos , Programas de Rastreamento/normas , Prognóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/fisiopatologia , China/epidemiologia , Análise por Conglomerados , Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Programas de Rastreamento/métodos , Mapas de Interação de Proteínas/genética , Análise de Sobrevida
7.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(7): 1126-1137, 2020 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-32741183

RESUMO

Objective: The objective of the study was systematically summarized the current status of the hepatocellular carcinoma (HCC) screening guidelines, and evaluated the HCC screening guidelines according to the authoritative framework of cancer screening guidelines of authoritative institutions, which provided important value for the formulation of HCC screening evidence-based guidelines. Methods: Literature search was conducted in multiple databases from their inception dates to January 3, 2019. In addition, we sought relevant websites further was searched to identify potentially eligible studies. Two reviewers independently screened literature and extracted data. Qualitative description of the basic information, recommendations of HCC screening, source of evidence and update progress of the HCC screening guidelines was conducted. Results: At present, there were no independent HCC screening guidelines worldwide. There were only 17 clinical practice HCC guidelines briefly provided the recommendation of HCC screening. Current HCC screening guidelines only recommended screening for high-risk groups of HCC. All guidelines have identified patients with chronic hepatitis B, hepatitis C and cirrhosis as high-risk groups for HCC. Most of guidelines recommended screening intervals was 6 months. The latest guidelines in Europe and the United States recommended ultrasound for screening HCC. The combination of ultrasound and AFP was recommended in the Asian guidelines. Currently, HCC screening guidelines mainly recommended screening strategies based on factors such as risk of HCC, accuracy of screening modality, screening cost, etc.. The key factors such as screening efficacy and safety have not yet been considered comprehensively. Conclusions: There were no independent HCC screening guidelines worldwide. Only some clinical practice HCC guidelines briefly mentioned HCC screening. Currently, the guidelines only recommend screening for high-risk groups of HCC, with a screening interval of 6 months. There are differences in screening modalities recommended by European, American and Asian guidelines for screening HCC. It is suggested that the relevant institutions should formulate the evidence-based HCC screening guidelines by referring to the theoretical framework of other authoritative other cancer screening guidelines.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer , Neoplasias Hepáticas/diagnóstico , Guias de Prática Clínica como Assunto , Ásia , Europa (Continente) , Humanos , Estados Unidos
8.
PLoS One ; 15(8): e0237475, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790728

RESUMO

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) exert high anti-HCV activity and are expected to show anti-inflammatory effects associated with HCV elimination. Furthermore, hepatocellular carcinoma (HCC) is known to dedifferentiate from hypovascular tumors, such as dysplastic nodules or well-differentiated HCC, to hypervascular tumors. We therefore explored whether or not DAAs can suppress the growth and hypervascularization of hypovascular tumors. METHODS: We enrolled 481 patients with HCV genotype 1 infection who were treated with Daclatasvir and Asunaprevir therapy. Of these, 29 patients had 33 hypovascular tumors, which were confirmed by contrast-enhanced MRI or CT before therapy. We prospectively analyzed the cumulative incidence of HCC, i.e. the growth or hypervascularization of hypovascular tumors, and compared the HCC development rates between patients with hypovascular tumors and those without any tumors. RESULTS: The mean size of the hypovascular tumors was 11.3 mm. Twenty seven of 29 patients who achieved an SVR had 31 nodules, 19 of 31 nodules (61.3%) showed tumor growth or hypervascularization, and 12 (38.7%) nodules showed no change or improvement. The cumulative incidence rates of tumor growth or hypervascularization were 19.4% at 1 year, 36.0% at 2 years, 56.6% at 3 years, and 65.3% at 4 years. Among the patients who achieved a sustained virologic response, the cumulative HCC development rates of patients with hypovascular tumors was significantly higher than in those without any tumors. A Cox proportional hazard analysis showed that a history of HCC therapy, the presence of a hypovascular tumor, and AFP >4.6 ng/mL at the end of treatment were independent risk factors for HCC development. CONCLUSION: Hypovascular tumors developed into HCC at a high rate despite the elimination of HCV by DAAs. As patients with hypovascular tumors were shown to have a high risk of HCC development, they should undergo strict HCC surveillance.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Imidazóis/uso terapêutico , Incidência , Isoquinolinas/uso terapêutico , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , alfa-Fetoproteínas/análise
10.
Life Sci ; 257: 118131, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32710948

RESUMO

AIMS: ATP-binding cassette (ABC) transporters constitute one of the largest families of membrane proteins in most organisms; however, their functions in hepatocellular carcinoma (HCC) remain unclear. MAIN METHODS: A set of bioinformatic tools was integrated to analyze the expression of 49 members of the ABC transporter family. The function of members which had prognostic values in HCC was explored by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. KEY FINDINGS: ABCA8 and ABCA9 were significantly down-regulated in HCC. Prognostic analysis indicated that HCC patients with low expression of ABCA8 and ABCA9 had significantly shorter survival time. On the contrary, ABCB6 was over-expressed in the disease and high expression of ABCB6 was associated with worse prognosis. Co-expression analysis, and subsequently GO and KEGG analysis indicated that ABCA8 and ABCA9 might participate in the catabolic processes of multiple metabolites, while ABCB6 might regulate ferroptosis. SIGNIFICANCE: This study reveals a previously unrecognized function of ABCB6 in HCC, by regulating ferroptosis. Since ABCB6 is over-expressed in HCC and ferroptosis involves in cancer development, ABCB6 might be a promising therapeutic target in the disease.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Carcinoma Hepatocelular/metabolismo , Ferroptose , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Prognóstico , Mapas de Interação de Proteínas , Análise de Sobrevida
12.
PLoS One ; 15(6): e0234062, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497093

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal and malignant tumours worldwide. New therapeutic targets for HCC are urgently needed. CYCLOPS (copy number alterations yielding cancer liabilities owing to partial loss) genes have been noted to be associated with cancer-targeted therapies. Therefore, we intended to explore the effects of the CYCLOPS gene RBM17 on HCC oncogenesis to determine if it could be further used for targeted therapy. METHODS: We collected data on 12 types of cancer from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) queries for comparison with adjacent non-tumour tissues. RBM17 expression levels, clinicopathological factors and survival times were analysed. RNAseq data were downloaded from the Encyclopaedia of DNA Elements database for molecular mechanism exploration. Two representative HCC cell models were built to observe the proliferation capacity of HCC cells when RBM17 expression was inhibited by shRBM17. Cell cycle progression and apoptosis were also examined to investigate the pathogenesis of RBM17. RESULTS: Based on 6,136 clinical samples, RBM17 was markedly overexpressed in most cancers, especially HCC. Moreover, data from 442 patients revealed that high RBM17 expression levels were related to a worse prognosis. Overexpression of RBM17 was related to the iCluster1 molecular subgroup, TNM stage, and histologic grade. Pathway analysis of RNAseq data suggested that RBM17 was involved in mitosis. Further investigation revealed that the proliferation rates of HepG2 (P = 0.003) and SMMC-7721 (P = 0.030) cells were significantly reduced when RBM17 was knocked down. In addition, RBM17 knockdown also arrested the progression of the cell cycle, causing cells to halt at the G2/M phase. Increased apoptosis rates were also found in vitro. CONCLUSION: These results suggest that RBM17 is a potential therapeutic target for HCC treatment.


Assuntos
Carcinoma Hepatocelular/genética , Variações do Número de Cópias de DNA , Neoplasias Hepáticas/genética , Fatores de Processamento de RNA/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Prognóstico , Fatores de Processamento de RNA/deficiência
13.
PLoS One ; 15(6): e0234084, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497121

RESUMO

Hepatocellular carcinoma (HCC), which is associated with an absence of obvious symptoms and poor prognosis, is the second leading cause of cancer death worldwide. Genome-wide molecular biology studies should provide biological insights into HCC development. Based on the importance of phosphorylation for signal transduction, several protein kinase inhibitors have been developed that improve the survival of cancer patients. However, a comprehensive database of HCC-related phosphorylated biomarkers (HCCPMs) and novel HCCPMs prediction platform has been lacking. We have thus constructed the dBMHCC databases to provide expression profiles, phosphorylation and drug information, and evidence type; gathered information on HCC-related pathways and their involved genes as candidate HCC biomarkers; and established a system for evaluating protein phosphorylation and HCC-related biomarkers to improve the reliability of biomarker prediction. The resulting dBMHCC contains 611 notable HCC-related genes, 234 HCC-related pathways, 17 phosphorylation-related motifs and their 255 corresponding protein kinases, 5955 HCC biomarkers, and 1077 predicted HCCPMs. Methionine adenosyltransferase 2B (MAT2B) and acireductone dioxygenase 1 (ADI1), which regulate HCC development and hepatitis C virus infection, respectively, were among the top 10 HCCPMs predicted by dBMHCC. Platelet-derived growth factor receptor alpha (PDGFRA), which had the highest evaluation score, was identified as the target of one HCC drug (Regorafenib), five cancer drugs, and four non-cancer drugs. dBMHCC is an open resource for HCC phosphorylated biomarkers, which supports researchers investigating the development of HCC and designing novel diagnosis methods and drug treatments. Database URL: http://predictor.nchu.edu.tw/dBMHCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Biologia Computacional/métodos , Bases de Dados Factuais , Neoplasias Hepáticas/metabolismo , Animais , Carcinoma Hepatocelular/diagnóstico , Humanos , Internet , Neoplasias Hepáticas/diagnóstico , Camundongos , Fosforilação , Prognóstico
14.
Eur J Endocrinol ; 183(3): R57-R73, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32508312

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a growing health problem with a global prevalence of over 25% and prevalence rates of over 60% in high-risk populations. It is considered the hepatic component of the metabolic syndrome and is associated with an increased risk of the development of various liver-associated and cardiometabolic complications. Given the complexity of NAFLD and associated comorbidities and complications, treatment requires interventions from a variety of different healthcare specialties. However, many clinicians are currently insufficiently aware of the potential harm and severity of NAFLD and associated comorbidities, complications and the steps that should be taken when NAFLD is suspected. Recognizing which patients suffer from non-progressive simple steatosis, metabolically active NASH with high risk of developing cardiovascular disease and which patients have a high risk of developing cirrhosis and hepatocellular carcinoma is important. Unfortunately, this can be difficult and guidelines towards the optimal diagnostic and therapeutic approach are ambivalent. Here we review the pathogenesis, diagnostics and treatment of NAFLD and discuss how multidisciplinary care path development could move forward.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/cirurgia , Humanos , Fígado/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/cirurgia
15.
Cancer Sci ; 111(9): 3338-3349, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32506598

RESUMO

Exosomal long noncoding RNA (lncRNA) has been found to be associated with the development of cancers. However, the expression characteristics and the biological roles of exosomal lncRNAs in hepatocellular carcinoma (HCC) remain unknown. Here, by RNA sequencing, we found 9440 mRNAs and 8572 lncRNAs were differentially expressed (DE-) in plasma exosomes between HCC patients and healthy controls. Exosomal DE-lncRNAs displayed higher expression levels and tissue specificity, lower expression variability and splicing efficiency than DE-mRNAs. Six candidate DE-lncRNAs (fold change 6 or more, P ≤ .01) were high in HCC cells and cell exosomes. The knockdown of these candidate DE-lncRNAs significantly affected the migration, proliferation, and apoptosis in HCC cells. In particular, a novel DE-lncRNA, RP11-85G21.1 (lnc85), promoted HCC cellular proliferation and migration by targeted binding and regulating of miR-324-5p. More importantly, the level of serum lnc85 was highly expressed in both Alpha-fetoprotein (AFP)-positive and AFP-negative HCC patients and allowed distinguishing AFP-negative HCC from healthy control and liver cirrhosis (area under the receiver operating characteristic curve, 0.869; sensitivity, 80.0%; specificity, 76.5%) with high accuracy. Our finding offers a new insight into the association between the dysregulation of exosomal lncRNA and HCC, suggesting that lnc85 could be a potential biomarker of HCC.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ácidos Nucleicos Livres , Exossomos/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/genética , Adulto , Processamento Alternativo , Carcinoma Hepatocelular/diagnóstico , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , MicroRNAs , Pessoa de Meia-Idade , Fenótipo , RNA Mensageiro , Curva ROC , Análise de Sequência de RNA
16.
Zhonghua Zhong Liu Za Zhi ; 42(6): 469-473, 2020 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-32575942

RESUMO

Objective: To investigate the characteristics of contrast-enhanced ultrasound (CEUS) in alpha-fetoprotein (AFP)-negative recurrent small hepatocellular carcinoma (rsHCC). Methods: The imaging characteristics of CEUS were retrospectively analyzed in 132 lesions from 116 patients with rsHCC, including 59 lesions from 51 AFP-negative patients and 73 lesions from 65 AFP-positive patients. The hemodynamic parameters such as contrast-enhanced onset time, time-to-peak, isoenhancement start time, low-enhancement start time, and perfusion mode were compared between two groups. Results: The time-to-peak, isoenhancement start time, low-enhancement start time of AFP-negative group were significantly increased than those in AFP-positive group (23.22±5.08)s vs. (20.30±3.41)s, (59.44±39.75)s vs. (40.75±16.16)s, (102.89±44.45)s vs. (87.08±25.27)s (all of P<0.05). Meanwhile, the proportion of isoenhancement during the portal and late phases in AFP-negative group was significantly higher than those in AFP-positive group (59.3% vs. 37.0%, 16.9% vs. 4.1%; all of P<0.05). However, there was no significant difference between the two groups in the enhancement start time (14.87±6.00)s vs. (14.35±5.30)s (P>0.05) as well as isoenhancement proportion in the arterial phase (94.9% vs. 98.6%, P>0.05). Conclusions: The enhancement pattern of CEUS in AFP-negative rsHCC patients was "fast-in and slow-out" with a diverse and atypical trend. Recognizing its regular features will facilitate the early detection of AFP-negative rsHCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Neoplasias Hepáticas/diagnóstico por imagem , Ultrassonografia/métodos , Carcinoma Hepatocelular/diagnóstico , Humanos , Aumento da Imagem/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , alfa-Fetoproteínas
17.
J Cancer Res Clin Oncol ; 146(7): 1819-1827, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32356179

RESUMO

BACKGROUND: It has been shown that local ablative procedures enable downsizing, reduce drop-out from the waiting list and improve prognosis after liver transplantation. It is still unclear whether a response to the local ablative therapy is due to a favorable tumor biology or if a real benefit in tumor stabilization exists, particularly in complete pathological response. METHOD: Data of 163 HCC patients who underwent liver transplantation were extracted from our prospectively maintained registry. We analyzed the tumor load, pre-transplant α-fetoprotein levels, child stage aside the application and success of local ablative therapies as bridging procedures before transplantation. RESULTS: 87 patients received multiple and/or combined local therapies. In 20 cases, this resulted in a complete remission of the tumor as observed in the explant histology. The other 76 patients underwent no bridging procedure. The observed 5- and 10-year survival rates for patients with bridging were 67% and 47% and without bridging 56% and 46%, respectively. Tumor-related 10-year survival showed a statistically significant difference between both groups (81% versus 59%). In the multivariate analyses bridging, number of lesions and α-fetoprotein level showed an independent statistically significant influence on tumor-related survival in these patients. CONCLUSIONS: Successful local ablative therapy before liver transplantation is an independent statistically significant factor in long-term tumor-related survival for patients with HCC in cirrhosis and reduces tumor recurrences.


Assuntos
Técnicas de Ablação , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Técnicas de Ablação/métodos , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Transplante de Fígado , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Tomografia Computadorizada por Raios X , Resultado do Tratamento
18.
Crit Rev Oncol Hematol ; 151: 102968, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32416345

RESUMO

Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy worldwide. Despite advances in imaging techniques, early diagnosis and management remain very poor. The early diagnosis of HCC requires diagnostic and imaging technologies with high sensitivity and precise quantification ability and with no tissue penetration limit. Nanotechnology-based cancer imaging is a rapidly emerging research area with significant applications in the diagnosis and treatment of cancer, which we review here with application to HCC. Furthermore, we discuss the combination of functional nanotheranostics and magnetic resonance imaging (MRI) for targeted delivery of phytochemical therapeutics, chemotherapeutic drugs, RNAi-based therapeutics, and vaccinations. Finally, this review presents the importance of MRI biomarkers for monitoring HCC treatment response. The use of advanced nanotheranostics as MRI contrast agents for imaging, diagnosis and drug delivery may enhance HCC management and provide a new area of research in tumor imaging technology.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Polímeros/química , Antineoplásicos/administração & dosagem , Portadores de Fármacos , Humanos , Imagem por Ressonância Magnética , Nanotecnologia
19.
N Z Med J ; 133(1515): 25-34, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32438374

RESUMO

BACKGROUND: Regular surveillance for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B viral (HBV) infection and hepatitis C (HCV) cirrhosis improves survival by earlier detection of the cancer at an earlier stage when curative intervention may still be possible. We compared patient characteristics, surveillance history and outcomes in patients presenting with advanced HCC secondary to HBV and HCV. METHOD: In this retrospective study, clinical databases and notes were reviewed in all cases of advanced HCC related to HBV or HCV referred to the tertiary HCC service in Auckland, New Zealand between 1 January 2003 and 31 December 2017. RESULTS: Over the 15-year period, 368 patients were referred with advanced HCC secondary to HBV (HBV-HCC) and 278 secondary to HCV (HCV-HCC), representing over 50% of all cases of HCC cases secondary to viral hepatitis. Of these 646 patients with advanced HCC, 75% of patients were not receiving guideline-recommended surveillance. More patients with advanced HBV-HCC were diagnosed with HCC prior to the diagnosis of HBV, compared to patients with advanced HCV-HCC (40% vs 28%, p<0.01). Fewer patients with previously diagnosed HBV infection were undergoing HCC surveillance than patients with previously diagnosed HCV infection (26% vs 42%, p<0.01). Late diagnosed patients had the worst outcomes, with 88% receiving palliative care and surviving on average only seven months (HBV five months vs HCV eight months, p=0.05). CONCLUSION: Survival in New Zealanders with hepatocellular carcinoma remains poor because the cancer is incurable in most patients at the time of detection. Because most cases are secondary to chronic hepatitis B and C infections, improved screening and linkage to antiviral therapy and HCC surveillance should improve outcomes.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Neoplasias Hepáticas/diagnóstico , Vigilância da População/métodos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/virologia , Diagnóstico Tardio , Detecção Precoce de Câncer , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Hepatite B Crônica/diagnóstico , Hepatite C Crônica/diagnóstico , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Cuidados Paliativos , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Taxa de Sobrevida
20.
PLoS One ; 15(5): e0232247, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32374744

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) continues to be a leading challenge in modern oncology. Early detection via blood-based screening tests has the potential to cause a stage-shift at diagnosis and improve clinical outcomes. Tumor associated autoantibodies (TA-AAbs) have previously shown the ability to distinguish HCC from patients with high-risk liver disease. This research aimed to further show the utility of TA-AAbs as biomarkers of HCC and assess their use in combination with Alpha-fetoprotein (AFP) for detection of HCC across multiple tumor stages. METHODS: Levels of circulating G class antibodies to 44 recombinant tumor associated antigens and circulating AFP were measured in the serum of patients with HCC, non-cancerous chronic liver disease (NCCLD) and healthy controls via enzyme-linked immunosorbent assay (ELISA). TA-AAb cut-offs were set at the highest Youden's J statistic at a specificity ≥95.00%. Panels of TA-AAbs were formed using net reclassification improvement. AFP was assessed at a cut-off of 200 ng/ml. RESULTS: Sensitivities ranged from 1.01% to 12.24% at specificities of 95.96% to 100.00% for single TA-AAbs. An ELISA test measuring a panel of 10 of these TA-AAbs achieved a combined sensitivity of 36.73% at a specificity of 89.89% when distinguishing HCC from NCCLD controls. At a cut-off of 200 ng/ml, AFP achieved a sensitivity of 31.63% at a specificity of 100.00% in the same cohort. Combination of the TA-AAb panel with AFP significantly increased the sensitivity for stage one (40.00%) and two (55.00%) HCC over the TA-AAb panel or AFP alone. CONCLUSIONS: A panel of TA-AAbs in combination with AFP could be clinically relevant as a replacement for measuring levels of AFP alone in surveillance and diagnosis strategies. The increased early stage sensitivity could lead to a stage shift with positive prognostic outcomes.


Assuntos
Antígenos de Neoplasias/imunologia , Autoanticorpos/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Feminino , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
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