Liu Donghong, Zhou Xinyu, Zhao Jun
Department of Special Medical Care, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, China.
Department of Epidemiology, Naval Medical University, Shanghai, 200433, China.
J Cancer. 2024 Jun 11;15(13):4287-4300. doi: 10.7150/jca.95730. eCollection 2024.
Hepatocellular carcinoma (HCC) is the main type of primary liver cancer, and its related death ranks third worldwide. The curative methods and progress prediction markers of HCC are not sufficient enough. Nevertheless, little progress has been made in the signature of mA-, mC-, mA-, mG-, and DNA methylation of HCC. We calibrated a risk gene signature model that can be used to categorize HCC patients based on univariate, multivariate, and LASSO Cox regression analysis. This gene signature classified the patients into high- and low-risk subgroups. Patients in the high-risk group showed significantly reduced overall survival (OS) compared with patients in the low-risk group. The gene set variation analysis (GSVA), immune infiltration, and immunotherapy response were analyzed. The results demonstrated that an immunosuppressive environment was exited and the high-risk group had higher sensitivity to 5-fluorouracil, cisplatin, sorafenib, tamoxifen, and epirubicin. These results indicated personalized therapy should be taken into consideration. Our findings enriched our understanding of the molecular heterogeneity, tumor microenvironment (TME), and drug susceptibility of HCC. mA-, mC-, mA-, mG-, and DNA methylation-related regulators may be promising biomarkers for future research.
肝细胞癌(HCC)是原发性肝癌的主要类型,其相关死亡在全球排名第三。HCC的治疗方法和进展预测标志物还不够充分。然而,HCC的mA、mC、mA、mG和DNA甲基化特征方面进展甚微。我们校准了一个风险基因特征模型,该模型可用于基于单变量、多变量和LASSO Cox回归分析对HCC患者进行分类。这种基因特征将患者分为高风险和低风险亚组。与低风险组患者相比,高风险组患者的总生存期(OS)显著缩短。对基因集变异分析(GSVA)、免疫浸润和免疫治疗反应进行了分析。结果表明存在免疫抑制环境,高风险组对5-氟尿嘧啶、顺铂、索拉非尼、他莫昔芬和表柔比星具有更高的敏感性。这些结果表明应考虑个性化治疗。我们的研究结果丰富了我们对HCC分子异质性、肿瘤微环境(TME)和药物敏感性的理解。mA、mC、mA、mG和DNA甲基化相关调节因子可能是未来研究中有前景的生物标志物。