Table_7_A FITM1-Related Methylation Signature Predicts the Prognosis of Patients With Non-Viral Hepatocellular Carcinoma.xlsx

Although great progress has been made in treatment against hepatitis virus infection, the prognosis of hepatocellular carcinoma (HCC) remains unsatisfied. Therefore, there is an unmet need to explore biomarkers or prognostic models for monitoring non-viral hepatocellular carcinoma. Accumulating evidence indicates that DNA methylation participates in carcinogenesis of malignancies. In the present study, we analyzed 101 non-viral HCC patients from TCGA database to figure out methylation-driven genes (MDGs) that might get involved in non-viral HCC pathogenesis using MethyMix algorithm. Then we picked out 8 key genes out of 137 MDGs that could affect the overall survival (OS) of both methylation and expression level. Using PCA, Uni-variate, Multi-variate, and LASSO cox regression analyses, we confirmed the potential prognostic value of these eight epigenetic genes. Ultimately, combined with immunohistochemistry (IHC), ROC, OS, and GSEA analyses, fat storage-inducing transmembrane protein1 (FITM1) was identified as a novel tumor suppressor gene in non-viral HCC and an applicable FITM1-methylation-based signature was built in a training set and validated in a testing set. Briefly, our work provides several potential biomarkers, especially FITM1, as well as a new method for disease surveillance and treatment strategy development.

尽管在治疗肝炎病毒感染方面取得了显著的进展，但肝细胞癌（HCC）的预后仍然不尽人意。因此，探索监测非病毒性肝细胞癌的生物标志物或预后模型的需求尚未得到满足。越来越多的证据表明，DNA甲基化参与了恶性肿瘤的发生发展。在本研究中，我们通过MethyMix算法分析了来自TCGA数据库的101例非病毒性HCC患者，以确定可能参与非病毒性HCC发病机制的甲基化驱动基因（MDGs）。随后，我们从137个MDGs中筛选出8个关键基因，这些基因可能影响甲基化和表达水平下的总生存期（OS）。通过主成分分析（PCA）、单变量、多变量和LASSO Cox回归分析，我们证实了这八个表观遗传基因的潜在预后价值。最终，结合免疫组化（IHC）、ROC、OS和GSEA分析，我们发现脂肪储存诱导的跨膜蛋白1（FITM1）作为一种新型的肿瘤抑制基因，在非病毒性HCC中具有显著作用，并在训练集和测试集中构建了一个基于FITM1甲基化的可应用特征。简而言之，我们的研究提供了几个潜在的生物标志物，特别是FITM1，以及一种新的疾病监测和治疗策略开发方法。