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1.
Hepatol Commun ; 6(1): 223-236, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34558830

RESUMO

Prognosis of hepatocellular carcinoma (HCC) could be affected by lack of or delayed therapy. We aimed to characterize the prevalence, correlates, and clinical impact of therapeutic underuse and delay in patients with HCC. Patients with HCC diagnosed between 2010 and 2017 were analyzed from the United States National Cancer Database. Logistic regression analysis identified factors associated with no and delayed (>90 days after diagnosis) HCC treatment. Cox proportional hazards regression with landmark analysis assessed the association between therapeutic delay and overall survival (OS), accounting for immortal time bias. Of 116,299 patients with HCC, 24.2% received no treatment and 18.4% of treated patients had delayed treatment. Older age, Black, Hispanic, lower socioeconomic status, earlier year of diagnosis, treatment at nonacademic centers, Northeast region, increased medical comorbidity, worse liver dysfunction, and higher tumor burden were associated with no treatment. Among treated patients, younger age, Hispanic, Black, treatment at academic centers, West region, earlier tumor stage, and receipt of noncurative treatment were associated with treatment delays. In multivariable Cox regression with a landmark of 150 days, patients with and without treatment delays had similar OS (adjusted hazard ratio [aHR], 1.01; 95% confidence interval [CI], 0.98-1.04) with a median survival of 33.7 vs. 32.1 months, respectively. However, therapeutic delay was associated with worse OS in patients who had tumor, nodes, and metastases (TNM) stage 1 (aHR, 1.06; 95% CI, 1.01-1.11) or received curative treatment (aHR, 1.12; 95% CI, 1.05-1.18). Conclusion: One-fourth of patients with HCC receive no therapy and one-fifth of treated patients experience treatment delays. Both were associated with demographic, socioeconomic, and clinical characteristics of patients as well as facility type and region. The association between therapeutic delay and survival was stage and treatment dependent.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Tempo para o Tratamento , Idade de Início , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etnologia , Carcinoma Hepatocelular/mortalidade , Feminino , Disparidades em Assistência à Saúde , Humanos , Cobertura do Seguro , Seguro Saúde , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Classe Social , Carga Tumoral , Estados Unidos/epidemiologia
2.
J Healthc Eng ; 2022: 6365485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463655

RESUMO

Due to the heterogeneity of tumors, we do not understand the given effect of pyroptosis on hepatocellular carcinoma (HCC) fully, particularly its influences on prognosis. The paper aims at exploring the prognostic value of pyroptosis-associated genes and its role in immune status in HCC. A multigene prognostic signature is set up by utilizing the least absolute shrinkage and choosing operator Cox exploration. The comparison of survival between different risk groups is made with the Kaplan-Meier exploration and Cox regression. LASSO Cox regression analysis is adopted to set up a pyroptosis-associated gene signature (CEP55 and MMP1). By comparing with the group at low risks, the high-risk group displayed greatly decreased OS. The fatidic ability of the prognostic gene signature is confirmed by the receiver-running feature curve analysis. According to multivariate Cox exploration, the risk mark is an independent predicting agent for OS. A new signature established with two pyroptosis-associated genes can be adopted for prognostic forecast and influence the immune situation in HCC.


Assuntos
Carcinoma Hepatocelular , Proteínas de Ciclo Celular , Neoplasias Hepáticas , Metaloproteinase 1 da Matriz , Piroptose , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Proteínas de Ciclo Celular/genética , Perfilação da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Metaloproteinase 1 da Matriz/genética , Piroptose/genética
3.
BMC Cancer ; 22(1): 249, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35255845

RESUMO

BACKGROUND: Inflammation plays a significant role in tumour development, progression, and metastasis. In this study, we focused on comparing the predictive potential of inflammatory markers for overall survival (OS), recurrence-free survival (RFS), and 1- and 2-year RFS in hepatocellular carcinoma (HCC) patients. METHODS: A total of 360 HCC patients were included in this study. A LASSO regression analysis model was used for data dimensionality reduction and element selection. Univariate and multivariate Cox regression analyses were performed to identify the independent risk factors for HCC prognosis. Nomogram prediction models were established and decision curve analysis (DCA) was conducted to determine the clinical utility of the nomogram model. RESULTS: Multivariate Cox regression analysis indicated that the prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR) were independent prognostic factors of OS, and aspartate aminotransferase-to-platelet ratio (APRI) was a common independent prognostic factor among RFS, 1-year RFS, and 2-year RFS. The systemic inflammation response index (SIRI) was an independent prognostic factor for 1-year RFS in HCC patients after curative resection. Nomograms established and achieved a better concordance index of 0.772(95% CI: 0.730-0.814), 0.774(95% CI: 0.734-0.815), 0.809(95% CI: 0.766-0.852), and 0.756(95% CI: 0.696-0.816) in predicting OS, RFS, 1-year RFS, and 2-year RFS respectively. The risk scores calculated by nomogram models divided HCC patients into high-, moderate- and low-risk groups (P < 0.05). DCA analysis revealed that the nomogram models could augment net benefits and exhibited a wider range of threshold probabilities in the prediction of HCC prognosis. CONCLUSIONS: The nomograms showed high predictive accuracy for OS, RFS, 1-year RFS, and 2-year RFS in HCC patients after surgical resection. The nomograms could be useful clinical tools to guide a rational and personalized treatment approach and prognosis judgement.


Assuntos
Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Nomogramas , Medição de Risco/métodos , Idoso , Aspartato Aminotransferases/sangue , Biomarcadores/análise , Plaquetas/metabolismo , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Bases de Dados Factuais , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
4.
BMC Cancer ; 22(1): 270, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35287627

RESUMO

PURPOSE: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with camrelizumab (hereafter, TACE-camrelizumab) in the treatment of patients with recurrent hepatocellular carcinoma (R-HCC) after curative resection. PATIENTS AND METHODS: R-HCC patients who underwent TACE plus camrelizumab or TACE-alone from January 2016 to August 2021 were retrospectively evaluated. Patients were assessed for tumor response, progression-free survival, survival rates and adverse events. RESULTS: Seventy-one patients were included in this study, including 20 patients in the TACE- camrelizumab group and 51 patients in the TACE-alone group. The objective response rate was 56.9% in the TACE-alone group and 40% in the TACE-camrelizumab group at 3 months (P = 0.201). The disease control rates were 84.3% in TACE-alone group and 80% in TACE-camrelizumab group at 3 months (P = 0.663). The progression-free survival (PFS) of the TACE-alone group was slightly longer than those of the TACE- camrelizumab group (9 months vs. 6 months). However, there were no statistically significant differences in the median PFS (P = 0.586). Similarly, there were no significant differences in the half-year and one-year survival rates (P = 0.304, P = 0.430). Multivariate analysis revealed that Neutrophil-to-lymphocyte ratio (NLR) was associated with PFS significantly. 75% patients developed at least one type of AEs related to camrelizumab in TACE-camrelizumab group, and no patients developed severe AEs. CONCLUSION: Comparing with TACE-Alone, the efficacy of TACE-camrelizumab for patients with R-HCC was similar. Meanwhile, the results of this study also indicated that TACE is still a better choice for patients with R-HCC.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Hepatectomia , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/mortalidade , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Período Pós-Operatório , Taxa de Sobrevida , Resultado do Tratamento
5.
BMC Cancer ; 22(1): 221, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35227234

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) has high incidence and mortality worldwide. Local ablation using radiofrequency ablation (RFA) or microwave ablation (MWA) is potentially curative for early-stage HCC with outcomes comparable to surgical resection. We explored the influence of demographic, clinical, and laboratory factors on outcomes of HCC patients receiving ablation. METHODS: This retrospective cohort study included 221 HCC patients receiving local ablation at Mayo Clinic between January 2000 and October 2018, comprising 140 RFA and 81 MWA. Prognostic factors determining overall survival (OS) and disease-free survival (DFS) were identified using multivariate analysis. RESULTS: There was no clinically significant difference in OS or DFS between RFA and MWA. In multivariate analysis of OS, pre-ablation lymphocyte-monocyte ratio [Hazard ratio (HR) 0.7, 95% confidence interval (CI) 0.58-0.84, P = 0.0001], MELD score [HR 1.12, 95%CI 1.068-1.17, P <  0.0001], tumor number [HR 1.23, 95%CI 1.041-1.46, P = 0.015] and tumor size [HR 1.18, 95%CI 1.015-1.37, P = 0.031] were clinically-significant prognostic factors. Among HCC patients with chronic hepatitis C (HCV) infection, positive HCV PCR at HCC diagnosis was associated with 1.4-fold higher hazard of death, with 5-year survival of 32.8% vs 53.6% in HCV PCR-negative patients. Regarding DFS, pre-ablation lymphocyte-monocyte ratio [HR 0.77, 95%CI 0.66-0.9, P = 0.001], MELD score [HR 1.06, 95%CI 1.022-1.11, P = 0.002], Log2 AFP [HR 1.11, 95%CI 1.033-1.2, P = 0.005], tumor number [HR 1.29, 95%CI 1.078-1.53, P = 0.005] and tumor size [HR 1.25, 95%CI 1.043-1.51 P = 0.016] were independently prognostic. CONCLUSIONS: Pre-ablation systemic inflammation represented by lymphocyte-monocyte ratio is significantly associated with OS and DFS in HCC patients treated with local ablation. HCV viremia is associated with poor OS. Tumor biology represented by tumor number and size are strongly prognostic for OS and DFS while AFP is significantly associated with DFS only.


Assuntos
Carcinoma Hepatocelular/sangue , Hepatite C Crônica/sangue , Mediadores da Inflamação/sangue , Neoplasias Hepáticas/sangue , Ablação por Radiofrequência , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Feminino , Hepacivirus , Hepatite C Crônica/complicações , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
6.
Dis Markers ; 2022: 5791471, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35280441

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, with high incidence and mortality rate. There is an urgent need to identify effective diagnostic and prognostic biomarkers for HCC. Members of the acidic leucine-rich nucleophosphoprotein 32 (ANP32) family, which mainly includes ANP32A, ANP32B, and ANP32E, are abnormally expressed and have prognostic value in certain cancers. However, the diagnostic, prognostic, and therapeutic value of ANP32 family members in HCC has not yet been fully studied. In this study, we identified the diagnostic and prognostic value of ANP32 family members in HCC. Transcriptome data from public databases, such as the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, suggested that ANP32A, ANP32B, and ANP32E were upregulated in HCC tissues, and high expression of ANP32 family members was associated with advanced pathologic stage and histologic grade. Our immunohistochemistry and western blot results further verified the differential expression of ANP32 family members. ANP32A, ANP32B, and ANP32E had an outstanding diagnostic potential. Survival analysis of HCC patients in TCGA databases demonstrated that ANP32A, ANP32B, and ANP32E were associated with poor overall survival (OS) and disease-specific survival (DSS). Univariate and multivariate Cox analyses suggested the capability of ANP32B and ANP32E to independently predict the OS and DSS of HCC patients. Gene set enrichment analysis (GSEA) showed that ANP32 family members were associated with immune response, epidermal cell differentiation, and stem cell proliferation. Expression of ANP32 family members was associated with immune cell infiltration and immune status in the tumor microenvironment of HCC, and patients with high ANP32 family expression had poor sensitivity to immunotherapy. Finally, we identified potential chemotherapy drugs for HCC patients with high ANP32 family expression by CellMiner database. This study suggested the diagnostic, prognostic, and therapeutic roles of the ANP32 family in HCC patients, providing potential therapeutic targets for HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/imunologia , Proteínas Nucleares/fisiologia , Proteínas de Ligação a RNA/fisiologia , Biomarcadores Tumorais , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
7.
J Immunol Res ; 2022: 1817694, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35224110

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) play an important role in many cancer progression. The aim of this study was to evaluate the expression level and clinical significance of the lncRNA, proliferating cell nuclear antigen pseudogene 1 (PCNAP1), in cancer tissue and the plasma of patients with hepatocellular carcinoma (HCC). METHODS: Quantitative real-time polymerase chain reaction was used to detect the expression of PCNAP1 in HCC tissue, adjacent tissue, and plasma. Spearman's rank correlation analysis was performed to assess relationships among cancer tissue, plasma PCNAP1, and plasma AFP. Kaplan-Meier analysis was used to assess survival of HCC patient with high and low expression of PCNAP1. The survival difference was compared by the log-rank test. The use of plasma levels PCNAP1 for diagnosing HCC was evaluated by receiver operating characteristic curve analysis. RESULTS: The expression of PCNAP1 in HCC tissue was significantly higher than in adjacent tissue (P < 0.01). The PCNAP1 levels were related to the TNM stage, lymph node metastasis, and tumor maximum diameter (P < 0.05) but were not related to gender and age (P = 0.459 and 0.656). Patients with greater levels of PCNAP1 had poorer survival than patients with lower levels of expression (P < 0.01). Compared to the healthy control group, a gastric cancer group, and a colorectal cancer group, HCC patient plasma levels of PCNAP1 were significantly greater (P < 0.01). The area under the curve (AUC) of plasma PCNAP1 in HCC patients was 0.83 (95% CI: 0.78-0.88). With a cut-off value of plasma PCNAP1 at 1.27, an HCC diagnostic sensitivity of 70.08%, and a specificity of 85.04%, was the maximum diagnostic efficiency achieved. CONCLUSION: This study demonstrates PCNAP1 levels to be increased in HCC patients. As such, PCNAP1 may be a new tool useful in disease diagnosis and prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , RNA Longo não Codificante/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Sensibilidade e Especificidade , Análise de Sobrevida , Regulação para Cima
8.
BMC Cancer ; 22(1): 175, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35172769

RESUMO

BACKGROUND: To evaluate the clinical outcomes of patients who received stereotactic body radiation therapy (SBRT) for single viable hepatocellular carcinoma (HCC) at the site of incomplete transarterial chemoembolization (TACE). METHODS: Patients treated with SBRT for single viable HCC after incomplete TACE between 2012 and 2017 at Asan Medical Center (Seoul, South Korea) were included. Incomplete TACE was defined as (1) evidence of viable HCC at the site of TACE on follow-up dynamic computed tomography (CT) or magnetic resonance imaging following one or more consecutive TACEs, (2) no definite tumor staining on superselective hepatic angiogram, or (3) no definite iodized oil uptake on post-embolization angiogram or CT. Doses of 10-15 Gy per fraction were given over 3-4 consecutive days. The primary outcome was local control rate at 3 years and secondary outcome included tumor response, overall survival rate, out-of-field intrahepatic recurrence-free survival, distant metastasis-free survival and treatment-related toxicities. Treatment-related adverse events were evaluated according to the common terminology criteria for adverse events, version 4.03. RESULTS: A total of 302 patients were analyzed. The median follow-up duration was 32.9 months (interquartile range [IQR], 23.6-41.7) and the median tumor size was 2.0 cm (range, 0.7-6.9). The local control (LC) and overall survival rates at 3 years were 91.2 and 72.7%, respectively. 95.4% of the tumors reached complete response (CR) during the entire follow-up period (anyCR). The median interval from SBRT to anyCR was 3.4 months (IQR, 1.9-4.7), and 39.9 and 83.3% of the lesions reached CR at 3- and 6-months after SBRT, respectively. Radiation-induced liver disease was observed in 8 (2.6%) patients. No patients experienced gastroduodenal bleeding within the radiation field. CONCLUSION: SBRT could be considered a feasible salvage treatment option for HCC after incomplete TACE.


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Radiocirurgia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Quimioembolização Terapêutica , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Radiocirurgia/métodos , República da Coreia , Estudos Retrospectivos , Terapia de Salvação , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
BMC Cancer ; 22(1): 185, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35180841

RESUMO

BACKGROUND: The number of young patients with hepatocellular carcinoma (HCC) is increasing, but whether patients of different ages have a survival advantage is unclear. This study was conducted to investigate whether age differences in the Barcelona Clinic Liver Cancer (BCLC) classification system contribute to the long-term survival outcomes of patients with HCC. METHODS: A total of 1602 patients with HCC admitted to the Beijing Ditan Hospital was included in this study. Patients were divided into younger (≤45 years) and older (> 45 years) groups. Factors determining overall survival and progression-free survival were analyzed using univariate and multivariate analyses with the Kaplan-Meier method and Cox proportional hazard regression model. We calculated the cumulative incidence function using the Fine-Gray model. The effect of mortality on age was also estimated using a restricted cubic spline. RESULTS: After matching, overall survival and progression-free survival were significantly better in younger patients than in older patients with BCLC stage 0-B (p = 0.015 and p = 0.017, respectively). In BCLC stage 0-B, all-cause mortality increased with age and increased rapidly around the age of 40 years (non-linear, p < 0.05). In BCLC stages 0-B, HCC-related and non-HCC-related deaths significantly differed between younger and older individuals (p = 0.0019). CONCLUSION: In stage BCLC 0-B, age affects the long-term prognosis of patients.


Assuntos
Fatores Etários , Carcinoma Hepatocelular/mortalidade , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Medição de Risco/estatística & dados numéricos , Adulto , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
10.
Mol Med ; 28(1): 16, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-35123387

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most common malignant tumors with poor survival. Pyroptosis is a kind of programmed cell death that can regulate the proliferation, invasion, and metastasis of tumor cells. However, the expression levels of pyroptosis-related genes (PRGs) in HCC and their relationship with prognosis are still unclear. METHODS: Our study identified 35 PRGs through bioinformatics analysis that were differentially expressed between tumor samples and nontumor samples. According to these differentially expressed genes, HCC patients could be divided into two groups, cluster 1 and cluster 2. The least absolute shrinkage and selection operator (LASSO) Cox regression method was performed to construct a 10-gene signature that classified HCC patients in the cancer genome atlas (TCGA) database into low-risk and high-risk groups. RESULTS: The results showed that the survival rate of HCC patients in the low-risk group was significantly higher than that in the high-risk group (p < 0.001). The validation cohort, the Gene Expression Omnibus (GEO) cohort, was divided into two risk groups based on the median risk score calculated by the TCGA cohort. The overall survival (OS) of the low-risk group was significantly better than that of the high-risk group (p = 0.007). Univariate and multivariate Cox regression analyses revealed that the risk score was an independent factor in predicting OS in HCC patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that immune-related high-risk groups were rich in genes and had reduced immune status. CONCLUSIONS: PRGs play a significant role in tumor immunity and have the potential capability to predict the prognosis of HCC patients.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Imunidade/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Piroptose/genética , Carcinoma Hepatocelular/diagnóstico , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Nomogramas , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Transcriptoma
11.
BMC Cancer ; 22(1): 142, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-35123420

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world. Although great advances in HCC diagnosis and treatment have been achieved, due to the complicated mechanisms in tumor development and progression, the prognosis of HCC is still dismal. Recent studies have revealed that the Warburg effect is related to the development, progression and treatment of various cancers; however, there have been a few explorations of the relationship between glycolysis and HCC prognosis. METHODS: mRNA expression profiling was downloaded from public databases. Gene set enrichment analysis (GSEA) was used to explore glycolysis-related genes (GRGs), and the LASSO method and Cox regression analysis were used to identify GRGs related to HCC prognosis and to construct predictive models associated with overall survival (OS) and disease-free survival (DFS). The relationship between the predictive model and the tumor mutation burden (TMB) and tumor immune microenvironment (TIME) was explored. Finally, real-time PCR was used to validate the expression levels of the GRGs in clinical samples and different cell lines. RESULTS: Five GRGs (ABCB6, ANKZF1, B3GAT3, KIF20A and STC2) were identified and used to construct gene signatures to predict HCC OS and DFS. Using the median value, HCC patients were divided into low- and high-risk groups. Patients in the high-risk group had worse OS/DFS than those in the low-risk group, were related to higher TMB and were associated with a higher rate of CD4+ memory T cells resting and CD4+ memory T cells activated. Finally, real-time PCR suggested that the five GRGs were all dysregulated in HCC samples compared to adjacent normal samples. CONCLUSIONS: We identified five GRGs associated with HCC prognosis and constructed two GRGs-related gene signatures to predict HCC OS and DFS. The findings in this study may contribute to the prediction of prognosis and promote HCC treatment.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Glicólise/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/metabolismo , Medição de Risco , Microambiente Tumoral/genética
12.
Hepatology ; 76(3): 589-598, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35124828

RESUMO

BACKGROUND AND AIMS: HCC is characterized by racial/ethnic disparities in rates. Recent USA reports suggest that incidence has begun to decline, but it is not clear whether the declines have occurred among all groups, nor whether mortality has declined. Thus, the current study examined USA incidence and mortality between 1992 and 2018. APPROACH & RESULTS: HCC incidence and incidence-based mortality data from the Surveillance, Epidemiology, and End Results program were used to calculate age-standardized rates by race/ethnicity, sex, and age. Trends were analyzed using joinpoint regression to estimate annual percent change (APC). Age-period-cohort models assessed the effects on trends of age, calendar period, and birth cohort. Overall, HCC incidence significantly declined between 2015 and 2018 (APC, -5.6%). Whereas most groups experienced incidence declines, the trends were most evident among Asians/Pacific Islanders, women, and persons <50 years old. Exceptions were the rates among non-Hispanic Black persons, which did not significantly decline (APC, -0.7), and among American Indians/Alaska Natives, which significantly increased (APC, +4.3%). Age-period-cohort modeling found that birth cohort had a greater effect on rates than calendar period. Among the baby boom cohorts, the 1950-1954 cohort had the highest rates. Similar to the overall incidence decline, HCC mortality rates declined between 2013 and 2018 (APC, -2.2%). CONCLUSIONS: HCC incidence and mortality rates began to decline for most groups in 2015, but persistent differences in rates continued to exist. Rates among non-Hispanic Black persons did not decline significantly, and rates among American Indians/Alaska Natives significantly increased, suggesting that greater effort is needed to reduce the HCC burden among these vulnerable groups.


Assuntos
Carcinoma Hepatocelular , Etnicidade , Disparidades nos Níveis de Saúde , Neoplasias Hepáticas , Grupos Raciais , Adulto , Carcinoma Hepatocelular/etnologia , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Incidência , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/mortalidade , Masculino , Mortalidade/etnologia , Mortalidade/tendências , Grupos Raciais/estatística & dados numéricos , Programa de SEER , Estados Unidos/epidemiologia
13.
Dis Markers ; 2022: 3533714, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35186165

RESUMO

OBJECTIVE: This study was aimed at exploring the prognostic and clinicopathological roles of aspartate aminotransferase-to-lymphocyte ratio index (ALRI) in patients with hepatocellular carcinoma via a meta-analysis. METHODS: The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases were comprehensively searched from inception to November 20, 2021. Pooled hazard ratio (HR) and corresponding 95% confidence interval (CI) were used to evaluate the relationship between ALRI and overall survival (OS) as well as progression-free survival (PFS) in patients with hepatocellular carcinoma. Odds ratio (OR) and the corresponding 95% CI were also used to investigate correlations between clinical factors and ALRI in patients with hepatocellular carcinoma. RESULTS: A total of 3914 patients with hepatocellular carcinoma from eleven retrospective cohorts were included in this meta-analysis. The combined results revealed that patients with hepatocellular carcinoma with elevated ALRI tended to have unfavorable OS (HR 1.53 [95% CI 1.25-1.82]; P < 0.001). Pooled HRs revealed that high ALRI was an independent risk factor for inferior PFS in patients with hepatocellular carcinoma (HR 1.36 [95% CI 1.10-1.63]; P < 0.001). In addition, high ALRI was strongly associated with male sex (OR 1.32 [95% CI 1.02-1.70]; P = 0.035), presence of cirrhosis (OR 1.68 [95% CI 1.01-2.81]; P = 0.046), larger tumor size (OR 2.25 [95% CI 1.31-3.88]; P < 0.001), presence of portal vein tumor thrombus (OR 2.50 [95% CI 1.52-4.11]; P < 0.001), and distant metastasis (OR 1.72 [95% CI 1.05-2.82]; P = 0.031). CONCLUSION: Elevated ALRI in patients with hepatocellular carcinoma predicted inferior survival outcomes and was strongly associated with some important features of hepatocellular carcinoma.


Assuntos
Aspartato Aminotransferases/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Linfócitos , Carcinoma Hepatocelular/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Contagem de Linfócitos , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
14.
BMC Cancer ; 22(1): 197, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35189839

RESUMO

BACKGROUND: DNA polymerase delta 1 catalytic subunit (POLD1) plays a key role in DNA replication and damage repair. A defective DNA proofreading function caused by POLD1 mutation contributes to carcinogenesis, while POLD1 overexpression predicts poor prognosis in cancers. However, the effect of POLD1 in hepatocellular carcinoma (HCC) is not well-understood. METHODS: Expression patterns of POLD1 were evaluated in TCGA and the HPA databases. Kaplan-Meier curves and Cox regression were used to examine the prognostic value of POLD1. The prognostic and predictive value of POLD1 was further validated by another independent cohort from ICGC database. The influences of DNA copy number variation, methylation and miRNA on POLD1 mRNA expression were examined. The correlation between infiltrating immune cells and POLD1 expression was analyzed. GO and KEGG enrichment analyses were performed to detect biological pathways associated with POLD1 expression in HCC. RESULTS: POLD1 was overexpressed in HCC (n = 369) compared with adjacent normal liver (n = 50). POLD1 upregulation was significantly correlated with positive serum AFP and advanced TNM stage. Kaplan-Meier and multivariate analyses suggested that POLD1 overexpression predicts poor prognosis in HCC. DNA copy gain, low POLD1 methylation, and miR­139-3p downregulation were associated with POLD1 overexpression. Besides, POLD1 expression was associated with the infiltration levels of dendritic cell, macrophage, B cell, and CD4 + T cell in HCC. Functional enrichment analysis suggested "DNA replication", "mismatch repair" and "cell cycle" pathways might be involved in the effect of POLD1 on HCC pathogenesis. Additionally, POLD1 mRNA expression was significantly associated with tumor mutation burden, microsatellite instability, and prognosis in various tumors. CONCLUSIONS: POLD1 may be a potential prognostic marker and promising therapeutic target in HCC.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , DNA Polimerase III/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Idoso , Biomarcadores Tumorais/genética , Variações do Número de Cópias de DNA/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Fígado/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , RNA Mensageiro/metabolismo
15.
Sci Rep ; 12(1): 1717, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35110551

RESUMO

The role of hepatocellular carcinoma (HCC) surveillance is being questioned in alcoholic cirrhosis because of the relative low HCC risk. This study aimed to assess the risk and predictors of HCC in Korean patients with alcoholic cirrhosis by using competing risk analysis. A total of 745 patients with alcoholic cirrhosis were recruited at a university-affiliated hospital in Korea and randomly assigned to either the derivation (n = 507) and validation (n = 238) cohort. Subdistribution hazards model of Fine and Gray was used with deaths and liver transplantation treated as competing risks. Death records were confirmed from Korean government databases. A nomogram was developed to calculate the Alcohol-associated Liver Cancer Estimation (ALICE) score. The cumulative incidence of HCC was 15.3 and 13.3% at 10 years for derivation and validation cohort, respectively. Age, alpha-fetoprotein level, and albumin level were identified as independent predictors of HCC and incorporated in the ALICE score, which discriminated low, intermediate, and high risk for HCC in alcoholic cirrhosis at the cut-off of 60 and 100. The risk of HCC can be stratified by using a combination of readily available clinical parameters (age, AFP level, and albumin level) in patients with alcoholic cirrhosis.


Assuntos
Carcinoma Hepatocelular/genética , Técnicas de Apoio para a Decisão , Cirrose Hepática Alcoólica/diagnóstico , Neoplasias Hepáticas/etiologia , Nomogramas , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Incidência , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática Alcoólica/mortalidade , Cirrose Hepática Alcoólica/cirurgia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , República da Coreia/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Albumina Sérica Humana/análise , alfa-Fetoproteínas/análise
16.
BMC Complement Med Ther ; 22(1): 21, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35078445

RESUMO

BACKGROUND: The aim of present study was to screen the novel and promising targets of curcumin in hepatocellular carcinoma diagnosis and chemotherapy. METHODS: Potential targets of curcumin were screened from SwissTargetPrediction, ParmMapper and drugbank databases. Potential aberrant genes of hepatocellular carcinoma were screened from Genecards databases. Fifty paired hepatocellular carcinoma patients' gene expression profiles from the GEO database were used to test potential targets of curcumin. Besides, GO analysis, KEGG pathway enrichment analysis and PPI network construction were used to explore the underlying mechanism of candidate hub genes. ROC analysis and Kaplan-Meier analysis were used to evaluate the diagnostic and prognostic value of candidate hub genes, respectively. Real-time PCR was used to verify the results of bioinformatics analysis. RESULTS: Bioinformatics analysis results suggested that AURKA, CDK1, CCNB1, TOP2A, CYP2B6, CYP2C9, and CYP3A4 genes served as candidate hub genes. AURKA, CDK1, CCNB1 and TOP2A were significantly upregulated and correlated with poor prognosis in hepatocellular carcinoma, AUC values of which were 95.7, 96.9, 98.1 and 96.1% respectively. There was not significant correlation between the expression of CYP2B6 and prognosis of hepatocellular carcinoma, while CYP2C9 and CYP3A4 genes were significantly downregulated and correlated with poor prognosis in hepatocellular carcinoma. AUC values of CYP2B6, CYP2C9, and CYP3A4 were 96.0, 97.0 and 88.0% respectively. In vitro, we further confirmed that curcumin significantly downregulated the expression of AURKA, CDK1, and TOP2A genes, while significantly upregulated the expression of CYP2B6, CYP2C9, and CYP3A4 genes. CONCLUSIONS: Our results provided a novel panel of AURKA, CDK1, TOP2A, CYP2C9, and CYP3A4 candidate genes for curcumin related chemotherapy of hepatocellular carcinoma.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Curcumina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Biologia Computacional , Mineração de Dados , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Fitoterapia , Valor Preditivo dos Testes , Mapas de Interação de Proteínas
17.
Anticancer Res ; 42(2): 867-876, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35093884

RESUMO

BACKGROUND/AIM: This study examined whether metformin can enhance the radiation response in a hepatocellular carcinoma (HCC) xenograft mice model and patient population. MATERIALS AND METHODS: Huh-7 human HCC-bearing xenograft mice were treated with gamma-ray, metformin, neutron therapy, and their combinations. Tumour growth and lung colonies were assessed. Overall, 145 patients who underwent radiotherapy for HCC were retrospectively analysed. RESULTS: The combinations of gamma-ray and metformin and neutron radiation and metformin inhibited tumour growth and metastatic lung nodule formation when compared to the monotherapy and gamma-ray groups, respectively. In patients who received radiotherapy for HCC, the overall survival rate was higher in the metformin-treated group than in the non-metformin group. CONCLUSION: Metformin inhibited tumour growth and metastasis in HCC by enhancing the radiation response in animal experiments. Additionally, metformin was also found to be associated with a higher survival outcome in patients with HCC.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Metformina/uso terapêutico , Animais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/radioterapia , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Raios gama/uso terapêutico , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Camundongos , Nêutrons/uso terapêutico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Oxid Med Cell Longev ; 2022: 4494713, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35069975

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, there is a lack of adequate means of treatment prognostication for HCC. Pyroptosis is a newly discovered way of programmed cell death. However, the prognostic role of pyroptosis in HCC has not been thoroughly investigated. Here, we generated a novel prognostic signature to evaluate the prognostic value of pyroptosis-related genes (PRGs) using the data from The Cancer Genome Atlas (TCGA) database. The accuracy of the signature was validated using survival analysis through the International Cancer Genome Consortium cohort (n = 231) and the First Affiliated Hospital of Wenzhou Medical University cohort (n = 180). Compared with other clinical factors, the risk score of the signature was found to be associated with better patient outcomes. The enrichment analysis identified multiple pathways related with pyroptosis in HCC. Furthermore, drug sensitivity testing identified six potential chemotherapeutic agents to provide possible treatment avenues. Interestingly, patients with low risk were confirmed to be associated with lower tumor mutation burden (TMB). However, patients at high risk were found to have a higher count of immune cells. Consensus clustering was performed to identify two main molecular subtypes (named clusters A and B) based on the signature. It was found that compared with cluster B, better survival outcomes and lower TMB were observed in cluster A. In conclusion, signature construction and molecular subtype identification of PRGs could be used to predict the prognosis of HCC, which may provide a specific reference for the development of novel biomarkers for HCC treatment.


Assuntos
Carcinoma Hepatocelular/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Hepáticas/genética , Piroptose/genética , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida
19.
BMC Cancer ; 22(1): 55, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35016637

RESUMO

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a role in the tumor microenvironment. Sorafenib, which inhibits the VEGF pathway, has an immune-modulation function but lacks substantial clinical data. This study aims to explore the efficacy of anti-PD-1 combined sorafenib in advanced hepatocellular carcinoma (HCC). METHODS: HCC patients who underwent anti-PD-1 treatment at Taipei Veterans General Hospital (Taipei, Taiwan) between January 2016 and February 2019 were reviewed. The efficacy was compared between groups after propensity-score matching. RESULTS: There were 173 HCC patients receiving anti-PD-1. After excluding unsuitable cases, 140 patients were analyzed, of which 58 received combination therapy and 82 received anti-PD-1 alone. The combination therapy had a trend of higher CR rate (8.6% vs. 4.9%, ns.), ORR (22.4% vs. 19.5%, ns.) and significantly higher DCR (69.0% vs. 37.8%, p < 0.05) comparing to anti-PD-1 alone. After matching, combination group achieved longer progression-free survival (3.87 vs. 2.43 months, p < 0.05) and overall survival (not reached vs. 7.17 months, p < 0.05) than anti-PD-1 alone, without higher grade 3/4 AE (10.3% vs. 7.1%, p = 0.73). The tumor response varied among different metastatic sites, with high responses in adrenal glands, peritoneum and lungs. The more AFP declined (> 10, > 50 and > 66%), the higher the ORR (70, 80 and 92%) and CR rates (30, 35 and 58%) were achieved at day 28. CONCLUSIONS: This is the first study to demonstrate the combination of anti-PD-1 and sorafenib had better efficacy and survival benefit. A prospective randomized study is needed to confirm this finding.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Hepáticas , Sorafenibe/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioterapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Pontuação de Propensão , Estudos Retrospectivos
20.
Cell Mol Life Sci ; 79(1): 70, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35018513

RESUMO

The histone methyltransferase SETD3 plays critical roles in various biological events, and its dysregulation is often associated with human diseases including cancer. However, the underlying regulatory mechanism remains elusive. Here, we reported that ubiquitin-specific peptidase 27 (USP27) promotes tumor cell growth by specifically interacting with SETD3, negatively regulating its ubiquitination, and enhancing its stability. Inhibition of USP27 expression led to the downregulation of SETD3 protein level, the blockade of the cell proliferation and tumorigenesis of hepatocellular carcinoma (HCC) cells. In addition, we found that USP27 and SETD3 expression is positively correlated in HCC tissues. Notably, higher expression of USP27 and SETD3 predicts a worse survival in HCC patients. Collectively, these data elucidated that a USP27-dependent mechanism controls SETD3 protein levels and facilitates its oncogenic role in liver tumorigenesis.


Assuntos
Carcinoma Hepatocelular/patologia , Proliferação de Células/fisiologia , Histona Metiltransferases/metabolismo , Neoplasias Hepáticas/patologia , Proteases Específicas de Ubiquitina/metabolismo , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Transformação Celular Neoplásica/patologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Células HEK293 , Histona Metiltransferases/genética , Humanos , Neoplasias Hepáticas/mortalidade , Proteases Específicas de Ubiquitina/genética , Ubiquitinação/fisiologia
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