Abstract
BackgroundThe potential reversibility of aberrant DNA methylation indicates an opportunity for oncotherapy. This study aimed to integrate methylation-driven genes and pretreatment prognostic factors and then construct a new individual prognostic model in hepatocellular carcinoma (HCC) patients.MethodsThe gene methylation, gene expression dataset and clinical information of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Methylation-driven genes were screened with a Pearson’s correlation coefficient less than − 0.3 and a P value less than 0.05. Univariable and multivariable Cox regression analyses were performed to construct a risk score model and identify independent prognostic factors from the clinical parameters of HCC patients. The least absolute shrinkage and selection operator (LASSO) technique was used to construct a nomogram that might act to predict an individual’s OS, and then C-index, ROC curve and calibration plot were used to test the practicability. The correlation between clinical parameters and core methylation-driven genes of HCC patients was explored with Student’s t-test.ResultsIn this study, 44 methylation-driven genes were discovered, and three prognostic signatures (LCAT, RPS6KA6, and C5orf58) were screened to construct a prognostic risk model of HCC patients. Five clinical factors, including T stage, risk score, cancer status, surgical method and new tumor events, were identified from 13 clinical parameters as pretreatment-independent prognostic factors. To avoid overfitting, LASSO analysis was used to construct a nomogram that could be used to calculate the OS in HCC patients. The C-index was superior to that from previous studies (0.75 vs 0.717, 0.676). Furthermore, LCAT was found to be correlated with T stage and new tumor events, and RPS6KA6 was found to be correlated with T stage.ConclusionWe identified novel therapeutic targets and constructed an individual prognostic model that can be used to guide personalized treatment in HCC patients.
Highlights
The potential reversibility of aberrant DNA methylation indicates an opportunity for oncotherapy
Construction of the risk score model To identify methylation-driven genes related to OS of hepatocellular carcinoma (HCC) patients, survival data of 329 HCC patients and 44 methylation-driven gene expression were integrated, and C5orf58, Lecithin-cholesterol acyltransferase (LCAT), ADH1B, Ribosomal protein S6 kinase A6 (RPS6KA6), SFN and ZDBF2 were identified with univariate Cox regression analysis
The 6 methylation-driven genes were significantly related to the OS of HCC patients
Summary
The potential reversibility of aberrant DNA methylation indicates an opportunity for oncotherapy. This study aimed to integrate methylation-driven genes and pretreatment prognostic factors and construct a new individual prognostic model in hepatocellular carcinoma (HCC) patients. Liver cancer is the sixth most common cancer and was the third major cause of cancer-related death in 2018 [1]. Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is the fourth most commonly diagnosed cancers in men and the fourth leading causes of cancer-related death among both women and men in China; the global incidence of HCC is predicted to exceed a million cases per year by 2025 [2, 3]. Surgical resection, ablative electrochemical therapies, chemoembolization, and radioembiolization are the most common treatments for HCC patients [4]. Exploring novel therapeutic targets and developing a prognosis module to guide personalized treatment are still needed
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