CHEK2 SNPs predict better prognosis in HBV-related hepatocellular carcinoma patients.
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ABSTRACT:
SUBMITTER: Wu H
PROVIDER: S-EPMC6958064 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
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Project description:BackgroundBoth persistent inflammatory activity and liver function damage contribute to a poor prognosis of hepatocellular carcinoma (HCC). This study aimed to develop nomograms that incorporate hepatitis virus B (HBV)-related peritumoral inflammation score (PIS) and liver function based on ALBI score to predict postoperative outcomes of HCC.MethodsThe prognostic roles of HBV-related preoperative PIS and ALBI scores in HCC recurrence were examined, and then two nomograms were constructed. The predictive accuracy and discriminative ability of the nomograms were compared with AJCC and BCLC staging systems of HCC.ResultsPIS (HBV-PIS) and ALBI scores (HBV-ALBI) with different HBV-DNA loads had association with overall survival (OS) and/or recurrence-free survival (RFS) of HCC. The independent predictors of OS and RFS were incorporated into the corresponding nomograms. In the training cohort, the C-indexes of OS and RFS nomograms were 0.751 and 0.736, respectively. ROC analyses showed that both OS and RFS nomograms had larger AUC (0.775 and 0.739, respectively) than AJCC and BCLC staging systems. These results were verified by the internal and external validation cohorts.ConclusionThe proposed nomograms, including HBV-DNA load-related PIS and ALBI scores, were accurate in predicting survival for HCC after curative resection.
| S-EPMC6171205 | biostudies-literature
Project description:Background: Hepatocellular carcinoma (HCC) is one of the most common aggressive solid malignant tumors and current research regards HCC as a type of metabolic disease. This study aims to establish a metabolism-related mRNA signature model for risk assessment and prognosis prediction in HCC patients. Methods: HCC data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Enrichment Analysis (GSEA) website. Least absolute shrinkage and selection operator (LASSO) was used to screen out the candidate mRNAs and calculate the risk coefficient to establish the prognosis model. A high-risk group and low-risk group were separated for further study depending on their median risk score. The reliability of the prediction was evaluated in the validation cohort and the whole cohort. Results: A total of 548 differential mRNAs were identified from HCC samples (n = 374) and normal controls (n = 50), 45 of which were correlated with prognosis. A total of 373 samples met the screening criteria and there were randomly divided into the training cohort (n = 186) and the validation cohort (n = 187). In the training cohort, six metabolism-related mRNAs were used to construct a prognostic model with a LASSO regression model. Based on the risk model, the overall survival rate of the high-risk cohort was significantly lower than that of the low-risk cohort. The results of a time-ROC curve proved that the risk score (AUC = 0.849) had a higher prognostic value than the pathological grade, clinical stage, age or gender. Conclusion: The model constructed by the six metabolism-related mRNAs has a significant value for survival prediction and can be applied to guide the evaluation of HCC and the designation of clinical therapy.
| S-EPMC8045485 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is one of the main causes of cancer deaths globally. Immunotherapy is becoming increasingly important in the cure of advanced HCC. Thus it is essential to identify biomarkers for treatment response and prognosis prediction. We searched publicly available databases and retrieved 465 samples of genes from The Cancer Genome Atlas (TCGA) database and 115 tumor samples from Gene Expression Omnibus (GEO). Meanwhile, we used the ImmPort database to determine the immune-related genes as well. Weighted gene correlation network analysis, Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were used to identify the key immune related genes (IRGs) which are closely related to prognosis. Gene set enrichment analysis (GSEA) was implemented to explore the difference of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway between Immune high- and low-risk score groups. Finally, we made a prognostic nomogram including Immune-Risk score and other clinicopathologic factors. A total of 318 genes from prognosis related modules were identified through weighted gene co-expression network analysis (WGCNA). 46 genes were strongly linked to prognosis after univariate Cox analysis. We constructed a seven genes prognostic signature which showed powerful prediction ability in both training cohort and testing cohort. 16 significant KEGG pathways were identified between high- and low- risk score groups using GSEA analysis. This study identified and verified seven immune-related prognostic biomarkers for the patients with HCC, which have potential value for immune modulatory and therapeutic targets.
| S-EPMC8139963 | biostudies-literature
Project description:This study aims to evaluate the predictive value of the prognostic nutritional index (PNI) and albumin-bilirubin grade (ALBI) for the postoperative prognosis of hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) patients undergoing radical hepatectomy (RH). Besides, we seek to identify novel prognosis indicators for HBV-HCC patients. Between April 2009 and March 2015, this work enrolled 868 patients diagnosed with HBV-HCC and undergoing RH in the Liver Surgery Department, West China Hospital, Sichuan University (WCHSU). The basic information, laboratory examination indicators, pathological reports, and follow-up data of patients were included. SPSS 22.0 statistical software was used for statistical data analyses. Platelet (PLT), alpha-fetoprotein (AFP), maximum diameter (max-D), number of tumors (Number), degree of differentiation (DD), Microvascular invasion situation (MVI), satellite focus situation (SF), PNI, and ALBI were the independent risk factors for both overall survival (OS) and disease-free survival (DFS) of HBV-HCC patients undergoing RH. Taking PNI = 46 and ALBI = - 2.80 as cut-off values, the OS and DFS of the PNI-high group were significantly higher than those of the PNI-low group. Meanwhile, the OS and DFS of the ALBI-low group were significantly higher than those of the ALBI-high group; the OS and DFS of the PNI-high + ALBI-low group were significantly higher than those of the PNI-low + ALBI-high group. Xie prognostic index (XPI) was the independent risk factor for both OS and DFS of HBV-HCC patients undergoing RH. The OS and DFS of the XPI-high group were significantly higher than those of the XPI-low group. This paper reveals that preoperative PNI and ALBI can predict the OS and DFS of HBV-HCC patients undergoing RH. Their impact on the prognosis of HBV-HCC patients is insignificant, however, it cannot be ignored. XPI can precisely predict the prognosis of HBV-HCC patients undergoing RH, nonetheless, its effect requires additional research for validation.
| S-EPMC8285529 | biostudies-literature
Project description:BACKGROUND:Recurrence prediction of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) present a great challenge because of a lack of biomarkers. Genetic variations play an important role in tumor development and metastasis. METHODS:Oligonucleotide microarrays were used to evaluate the genetic characteristics of tumor DNA in 30 HBV-related HCC patients who were underwent LT. Recurrence-related single-nucleotide polymorphism were selected, and their prognostic value was assessed and validated in two independent cohorts of HCC patients (N = 102 and N = 77), using pretransplant plasma circulating DNA. Prognostic significance was assessed by Kaplan-Meier survival estimates and log-rank tests. Multivariate analyses were performed to evaluate prognosis-related factors. RESULTS:rs894151 and rs12438080 were significantly associated with recurrence (P = .003 and P = .004, respectively). Multivariate analyses demonstrated that the co-index of the 2 SNPs was an independent prognostic factor for recurrence (P = .040). Similar results were obtained in the third cohort (N = 77). Furthermore, for HCC patients (all the 3 cohorts) exceeding Milan criteria, the co-index was a prognostic factor for recurrence and survival (P<.001 and P = .002, respectively). CONCLUSIONS:Our study demonstrated first that genetic variations of rs894151 and rs12438080 in pretransplant plasma circulating DNA are promising prognostic markers for tumor recurrence in HCC patients undergoing LT and identify a subgroup of patients who, despite having HCC exceeding Milan criteria, have a low risk of post-transplant recurrence.
| S-EPMC3187841 | biostudies-literature
Project description:The present study reveals an immunological characterization of circulating and tumor-infiltrating T follicular helper cells (Tfh), namely CXCR5+CD45RA-CD4+ T cells, and their related cytokines in hepatitis B virus-related hepatocellular carcinoma (HCC) patients. In HCC patients, circulating Tfh cells showed a CCR7+ and/or ICOS+ phenotype with increased Th2-like cells and decreased Th1-like and Th17-like subsets. Although the bulk frequency of circulating Tfh cells was not altered in HCC patients, the frequency of infiltrated CXCR5+CD45RA-CD4+ CD3+cells was higher in tumor than in para-tumor tissues, and Th1-like cells were the predominant phenotype. Circulating Tfh cells in HCC patients were defective in the production of IL-21 in vitro, which was in accordance with lower IL-21 levels in tumor tissues than in para-tumor tissues. Serum CXCL13 was increased in HCC patients and associated with recurrence-free survival after hepatectomy. This was confirmed in an additional HCC cohort of 111 patients with up to 5 years follow-up. Immunohistochemical staining indicated that the percentage of CXCR5+ or CXCL13+ cells was higher in poorly differentiated than in well-differentiated tumors. In conclusion, patients with HBV-related HCC showed altered phenotypes and impaired function of Tfh cells or subpopulations. CXCL13 could be a potential biomarker for predicting recurrence in HCC patients after hepatectomy.
| S-EPMC4792554 | biostudies-literature
Project description:To discuss the prognostic correlation between hepatitis B virus DNA (HBV DNA) level and HBV-related hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI).Data from HCC patients undergoing hepatectomy with pathological evidence of MVI were retrospectively collected and 1:1 propensity scoring matching (PSM) analysis was performed. According to the HBV DNA levels before and after surgery, the disease-free survival (DFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, and the Cox proportional hazards regression was used to analyze the risk factors associated with the postoperative prognosis. After 1:1 PSM, 139 pairs of patients were enrolled in the high preoperative HBV DNA level group (H group) and low preoperative HBV DNA level group (L group), and after operation, patients with high preoperative HBV DNA levels were divided into the persistently high HBV DNA level group (P group) and the decreased HBV DNA level group (D group).According to the multivariate analysis, the HBV DNA level of 2000 IU/ml or greater before operation was significantly associated with the DFS (hazard ratio, 1.322; 95%CI, 1.016-1.721) and OS (hazard ratio, 1.390; 95%CI, 1.023-1.888). A persistent HBV DNA level of 2,000 IU/ml or greater after operation was also the independent risk factor of DFS (hazard ratio, 1.421; 95%CI, 1.018-1.984) and OS (hazard ratio, 1.545; 95%CI, 1.076-2.219).For the HBV-related HCC patients with MVI, preoperative high HBV DNA copies are prognostication of poorer prognosis, and effective antivirus treatment would significantly improve the patients' prognosis.
| S-EPMC6635265 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most serious malignant tumors threatening human life with a high mortality rate. The liver regenerative capacity after hepatectomy in early-stage HCC patients is influenced by various factors, including surgical methods and energy metabolism. This study aims to provide a prognostic model based on genes related to liver regeneration that can predict the prognosis of non-tumor tissues in HCC patients.Patients and methodsA total of 584 non-tumor tissues from HCC patients were collected from three independent databases. Kaplan-Meier survival curves were used to identify prognostic liver-regeneration genes. Subsequently, a prognostic indicator, designated as the Liver Regeneration score (LR score), was determined using single-sample gene set enrichment analysis (ssGSEA). Independent cohorts were used to verify the relationship between LR score and prognosis in non-tumor tissues of HCC patients. Furthermore, a liver regeneration-related model was established to validate key genes identified through LASSO Cox regression analysis.ResultsWe constructed a gene set comprising 24 liver regeneration-related genes, and the LR score was utilized to predict the prognosis of HCC patients based on its levels in non-tumor tissues. In non-tumor tissues of HCC patients, higher LR scores were associated with improved prognosis. Higher LR scores in non-tumor tissues indicate improved liver metabolism in HCC patients, revealed by Enrichment analysis. LASSO Cox regression analysis identified two key genes, DHTKD1 (dehydrogenase E1 and transketolase domain containing 1) and PHYH (phytanoyl-CoA 2-hydroxylase), and higher expression levels of these genes in non-tumor tissues were correlated with better prognosis. The expression levels of these two genes also changed corresponding to the progression of liver regeneration.ConclusionIn summary, our study has introduced a novel LR gene signature for HCC patients, providing a predictive model for estimating clinical prognosis from non-tumor tissues. The LR score demonstrates promise as a reliable indicator for predicting overall survival in HCC.
| S-EPMC10712262 | biostudies-literature
Project description:BackgroundDefects of autophagy and endoplasmic reticulum (ER) stress are related to many diseases and tumors. However, only a few studies have examined hepatocellular carcinoma (HCC) as related to these processes. Therefore, in this study, we investigated the expression and extent of autophagy and ER stress-related markers in HCC and their influence on clinical characteristics and prognosis for each protein.MethodologyThe expression of autophagy-related markers (LC3 and Beclin-1) and ER stress-related markers (GRP78 and CHOP) was analyzed by immunohistochemistry on tissues from completely resected specimens of 190 HCC patients. Their influence on clinicopathologic features and prognosis were evaluated using the chi-square test and Kaplan-Meier analysis. Correlations of each protein were determined by Spearman's correlation analysis.Principal findingsLC3 expression was not correlated with TNM, BCLC stage, or Edmonson-Steiner grading, whereas it was correlated with longer overall survival (OS) (p = 0.039) and tended to be related with longer time to recurrence (TTR) (p=0.068) although it did not show statistical significance. Multivariate analysis indicated that LC3 expression was a significantly independent prognostic factor of OS (HR, 0.42; 95% CI, 0.22-0.80; p-value=0.009) and TTR (HR, 0.54; 95% CI, 0.33-0.90; p=0.017). Expression of LC3 in advanced stages of TNM (III) (p=0.045) and Edmonson-Steiner Grades (III and IV) (p=0.043) was correlated with longer survival, but not in the early stages. A positive correlation was not observed between the expression of autophagy-related markers and ER stress-related markers.ConclusionOur results suggest that the expression and extent of LC3 might be a strong prognostic factor of HCC, especially in patients with surgical resection.
| S-EPMC3839913 | biostudies-literature
Project description:Increased intracellular toxicity due to an imbalance in copper homeostasis caused by copper ion accumulation could regulate the rate of cancer cell growth and proliferation. The goal of this study was to create a novel Cuproptosis-related lncRNA signature that may be utilized to predict survival and immunotherapy in HCC patients. Cuproptosis-associated lncRNAs and differentially expressed lncRNAs between HCC tumor tissue and normal tissue were discovered first. By LASSO-Cox analysis, the overlapping lncRNAs were then utilized to build a Cuproptosis-associated lncRNA signature, which might be used to predict patient prognosis and responsiveness to immune checkpoint blockade (ICB) therapy. Differences in the infiltration of immune cell subpopulations between high and low-risk score subgroups were also analyzed. Moreover, a nomogram based on the Cuproptosis-associated lncRNA signature and clinical features was developed and demonstrated to have good predictive potential. Finally, qRT-PCR was performed in HerpG2 and MHCC-97H cell lines to explore whether these lncRNAs were indeed involved in the process of Cuproptosis. In summary, we created a prognostic lncRNA profile linked to Cuproptosis to forecast response to immunotherapy, which may provide a new potential non-apoptotic therapeutic perspective for HCC patients.
| S-EPMC9256635 | biostudies-literature