Regmi Parbatraj, He Zhi-Qiang, Lia Thongher, Paudyal Aliza, Li Fu-Yu
Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China.
Department of Uro Surgery, West China Hospital, Sichuan University, Chengdu, China.
Front Genet. 2022 Jun 6;13:918983. doi: 10.3389/fgene.2022.918983. eCollection 2022.
About 90% of liver cancer-related deaths are caused by hepatocellular carcinoma (HCC). N7-methylguanosine (m7G) modification is associated with the biological process and regulation of various diseases. To the best of our knowledge, its role in the pathogenesis and prognosis of HCC has not been thoroughly investigated. To identify N7-methylguanosine (m7G) related prognostic biomarkers in HCC. Furthermore, we also studied the association of m7G-related prognostic gene signature with immune infiltration in HCC. The TCGA datasets were used as a training and GEO dataset "GSE76427" for validation of the results. Statistical analyses were performed using the R statistical software version 4.1.2. Functional enrichment analysis identified some pathogenesis related to HCC. We identified 3 m7G-related genes (CDK1, ANO1, and PDGFRA) as prognostic biomarkers for HCC. A risk score was calculated from these 3 prognostic m7G-related genes which showed the high-risk group had a significantly poorer prognosis than the low-risk group in both training and validation datasets. The 3- and 5-years overall survival was predicted better with the risk score than the ideal model in the entire cohort in the predictive nomogram. Furthermore, immune checkpoint genes like CTLA4, HAVCR2, LAG3, and TIGT were expressed significantly higher in the high-risk group and the chemotherapy sensitivity analysis showed that the high-risk groups were responsive to sorafenib treatment. These 3 m7G genes related signature model can be used as prognostic biomarkers in HCC and a guide for immunotherapy and chemotherapy response. Future clinical study on this biomarker model is required to verify its clinical implications.
约90%的肝癌相关死亡由肝细胞癌（HCC）引起。N7-甲基鸟苷（m7G）修饰与多种疾病的生物学过程和调控相关。据我们所知，其在HCC发病机制和预后中的作用尚未得到充分研究。旨在鉴定HCC中与N7-甲基鸟苷（m7G）相关的预后生物标志物。此外，我们还研究了m7G相关预后基因特征与HCC免疫浸润的关系。使用TCGA数据集作为训练集，并使用GEO数据集“GSE76427”验证结果。使用R统计软件版本4.1.2进行统计分析。功能富集分析确定了一些与HCC相关的发病机制。我们鉴定出3个与m7G相关的基因（CDK1、ANO1和PDGFRA）作为HCC的预后生物标志物。根据这3个与m7G相关的预后基因计算出一个风险评分，结果显示在训练集和验证集中，高风险组的预后明显比低风险组差。在预测列线图中，整个队列使用风险评分预测3年和5年总生存率比理想模型更好。此外，CTLA4、HAVCR2、LAG3和TIGT等免疫检查点基因在高风险组中表达明显更高，化疗敏感性分析表明高风险组对索拉非尼治疗有反应。这3个与m7G基因相关的特征模型可作为HCC的预后生物标志物以及免疫治疗和化疗反应的指导。需要对该生物标志物模型进行未来的临床研究以验证其临床意义。
