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The combination of three molecular markers can be a valuable predictive tool for the prognosis of hepatocellular carcinoma patients.

ABSTRACT: Based on molecular profiling, several prognostic markers for HCC are also used in clinic, but only a few genes have been identified as useful. We collected 72 post-operative liver cancer tissue samples. Genes expression were tested by RT-PCR. Multilayer perceptron and discriminant analysis were built, and their ability to predict the prognosis of HCC patients were tested. Receiver operating characteristic (ROC) analysis was performed and multivariate analysis with Cox's Proportional Hazard Model was used for confirming the markers'predictive efficiency for HCC patients'survival. A simple risk scoring system devised for further predicting the prognosis of liver tumor patients. Multilayer perceptron and discriminant analysis showed a very strong predictive value in evaluating liver cancer patients'prognosis. Cox multivariate regression analysis demonstrated that DUOX1, GLS2, FBP1 and age were independent risk factors for the prognosis of HCC patients after surgery. Finally, the risk scoring system revealed that patients whose total score >1 and >3 are more likely to relapse and die than patients whose total score ≤1 and ≤3. The three genes model proposed proved to be highly predictive of the HCC patients' prognosis. Implementation of risk scoring system in clinical practice can help in evaluating survival of HCC patients after operation.

SUBMITTER: Chen SS

PROVIDER: S-EPMC4832332 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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The combination of three molecular markers can be a valuable predictive tool for the prognosis of hepatocellular carcinoma patients.

Chen Sheng-Sen SS Yu Kang-Kang KK Ling Qing-Xia QX Huang Chong C Li Ning N Zheng Jian-Ming JM Bao Su-Xia SX Cheng Qi Q Zhu Meng-Qi MQ Chen Ming-Quan MQ

Scientific reports 20160415

Based on molecular profiling, several prognostic markers for HCC are also used in clinic, but only a few genes have been identified as useful. We collected 72 post-operative liver cancer tissue samples. Genes expression were tested by RT-PCR. Multilayer perceptron and discriminant analysis were built, and their ability to predict the prognosis of HCC patients were tested. Receiver operating characteristic (ROC) analysis was performed and multivariate analysis with Cox's Proportional Hazard Model ...[more]

PMID: 27079415

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Project description:Hepatocellular carcinoma (HCC) is a worldwide malignant cancer with high incidence and mortality. Considering the high heterogeneity of HCC, clarifying molecular characteristics associated with HCC development could help improve patients' outcomes. Pyroptosis is a novel form of cell death and is noted to be implicated in HCC pathogenesis whereas its molecular feature in HCC is unclear. Thus, we intended to clarify the molecular characteristic as well as the clinical significance of pyroptosis for HCC. A systematic bioinformatics analysis was conducted among 40 pyroptosis-related genes based on The Cancer Genome Atlas, the International Cancer Genome Consortium, and the Gene Expression Omnibus databases. A total of 12 HCC-associated pyroptosis-related genes (HPRGs) were identified to be overexpressed in HCC tissues and significantly connected to patients' poor survival. Through consensus clustering based on the HPRGs' expression, we found patients could be stratified into two distinctive pyroptosis subtypes, PyLow and PyHigh. The PyHigh group owned a notable lower survival rate and a higher high-grade proportion compared with the PyLow subtype. Besides, patients' sensitivities to chemotherapeutic drugs also presented distinctive differences between the two subtypes. Indicated by pathway enrichment analysis and immune characteristic difference analysis, the distinctions between the pyroptosis subtypes may be related to tumor immunity. Further, a five-gene risk model composed of BAK1, CHMP4A, CHMP4B, DHX9, and GSDME was established. Subsequent analyses demonstrated that the model could credibly classify patients as low or high risk and was an independent prognostic indicator for HCC. Abnormal expressions of the five genes were validated by biological experiments and new bioinformatics analysis. In conclusion, this study recognized and verified two heterogeneous pyroptosis subtypes and a predictable prognosis model for HCC. Our work may help facilitate the clinical management and treatment of HCC and understand the functions of pyroptosis in oncology.

Project description:Purpose To test and compare the association between radiologic measurements of lesion diameter, volume, and enhancement on baseline magnetic resonance (MR) images with overall survival and tumor response in patients with unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). Materials and Methods This HIPAA-compliant retrospective, single-institution analysis was approved by the institutional review board, with waiver of informed consent. It included 79 patients with unresectable HCC who were treated with TACE. Baseline arterial phase contrast material-enhanced (CE) MR imaging was used to measure the overall and enhancing tumor diameters. A segmentation-based three-dimensional quantification of the overall and enhancing tumor volumes was performed in each patient. Numeric cutoff values (5 cm for diameters and 65 cm(3) for volumes) were used to stratify the patient cohort in two groups. Tumor response rates according to Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) guidelines were recorded for all groups. Survival was evaluated by using Kaplan-Meier analysis and was compared by using Cox proportional hazard ratios (HRs) after univariate and multivariate analysis. Results Stratification according to overall and enhancing tumor diameters did not result in a significant separation of survival curves (HR, 1.4; 95% confidence interval [CI]: 0.7, 2.5; P = .234; and HR, 1.6; 95% CI: 0.9, 2.8; P = .08, respectively). The stratification according to overall and enhancing tumor volume achieved significance (HR, 1.8; 95% CI: 0.9, 3.4; P = .022; and HR, 1.8; 95% CI: 1.1, 3.1; P = .017, respectively). As for tumor response, higher response rates were observed in smaller lesions compared with larger lesions, when the 5-cm threshold (27% vs 15% for mRECIST and 45% vs 24% for EASL) was used. Conclusion As opposed to anatomic tumor diameter as the most commonly used staging marker, volumetric assessment of lesion size and enhancement on baseline CE MR images is strongly associated with survival of patients with HCC who were treated with TACE.

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The combination of three molecular markers can be a valuable predictive tool for the prognosis of hepatocellular carcinoma patients.

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The combination of three molecular markers can be a valuable predictive tool for the prognosis of hepatocellular carcinoma patients.

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