甲基化驱动基因ZC2HC1A的表达对肝癌预后的影响以及与免疫浸润的关系

Effect of Expression of Methylation Driver Gene ZC2HC1A on Prognosis of Hepatocellular Carcinoma and Its Association with Immune Infiltration

摘要: 背景：肝细胞肝癌(HCC)是目前世界上发病率及死亡率较高的肿瘤，具有高度异质性，容易漏诊。本研究主要开发新的肿瘤标志物，提高HCC的诊断效能，为开发新型疗法提供新思路。方法：在癌症基因组图谱(TCGA)中下载HCC的表达数据和甲基化数据，筛选出甲基化驱动基因ZC2HC1A。分别在TCGA和ICGC (International Cancer Genome Consortium)数据库中研究ZC2HC1A的表达对HCC患者预后的影响。使用GSEA (Gene Set Enrichment Analysis)，预测ZC2HC1A的功能通路。分析ZC2HC1A的表达与肿瘤免疫微环境中免疫细胞、免疫调节因子的关系。结果：发现甲基化驱动基因ZC2HC1A在HCC的患者中高表达，其中高表达组的肿瘤分级、临床分期和T分期更晚，1、3、5年生存率较低，提示预后不佳。GSEA分析得出ZC2HC1A高表达组与癌症和免疫相关的信号通路相关。ZC2HC1A高表达组抗肿瘤细胞CD8+T细胞、NK细胞、肥大细胞消耗过多，而促肿瘤细胞M0巨噬细胞明显升高。结论：ZC2HC1A表达量能够评估HCC预后；初步探索了ZC2HC1A与免疫治疗的相关性，指导临床医生精准治疗，并有望成为新的治疗靶点。

Abstract: Background: Hepatocellular carcinoma (HCC) is a tumor with high morbidity and mortality in the world, which is highly heterogeneous and easy to be missed. The purpose of this study is to develop new tumor markers, improve the diagnostic efficiency of HCC, and provide new ideas for the devel-opment of new therapies. Methods: Expression and methylation data of HCC were downloaded from cancer Genome Atlas (TCGA), and DNA methylation-driven gene ZC2HC1A was screened. The effects of ZC2HC1A expression on the prognosis of HCC patients were investigated in TCGA and Internation-al Cancer Genome Consortium (ICGC) databases. Gene Set Enrichment Analysis (GSEA) was used to predict the functional pathway of ZC2HC1A. The relationship between the expression of ZC2HC1A and immune cells in the tumor immune microenvironment was analyzed. Results: It was found that methylation-driven gene ZC2HC1A was highly expressed in HCC patients, and the tumor grade, clin-ical stage and T stage of the high expression group were later, and the survival rate of 1, 3 and 5 years was lower, suggesting poor prognosis. GSEA analysis showed that high expression of ZC2HC1A was associated with cancer and immune-related signaling pathways. CD8+T cells, NK cells and mast cells were consumed too much in the group with high expression of ZC2HC1A, while M0 macro-phages of tumor cells were significantly increased. Conclusions: The expression level of ZC2HC1A can evaluate the prognosis of HCC. This study preliminarily explored the correlation between ZC2HC1A and immunotherapy, guided clinicians to precision treatment, and is expected to become a new therapeutic target.