Xing Jiyuan, Shen Shen, Dong Zihui, Hu Xiaobo, Xu Lixia, Liu Xiaorui, Li Qinggang, Zhang Yize, Cui Gangying, Yu Zujiang
Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Cell Dev Biol. 2021 Nov 10;9:761391. doi: 10.3389/fcell.2021.761391. eCollection 2021.
RNA modifications have emerged as important posttranscriptional changes in multiple tumor cellular processes and tumorigenesis, including hepatocellular carcinoma (HCC). However, the potential roles and the interaction between regulators of RNA modifications and the tumor microenvironment (TME) are unclear in HCC. The gene expression profiles of 26 RNA modification "writers" were investigated in the TCGA cohort. The unsupervised clustering approach was used to class these RNA modification regulators. The characteristics of immune cell infiltration from TME for each cluster was tested by the CIBERSORT method. Additionally, we established a scoring model to evaluate the RNA modification characteristics of individual tumors. The associations between the scoring model and genetic as well as clinical characteristics, drug sensitivity, and response to immunotherapy were also analyzed. We mapped the somatic mutations and somatic copy number variation of the RNA modification regulators. The expression of all selected regulators was detected, and two modification patterns were identified that featured distinct immune cell infiltration characteristics. Subsequently, we developed a score model (termed as WM-Score model). Furthermore, the survival analysis showed that the WM-Score value was associated with HCC patient prognosis. The results of the ROC curves analysis and multivariate analysis all confirmed that the WM-Score value was strongly associated with anti-cancer drug resistance and therapeutic efficacy of immunotherapy, thus could be used as an independent risk factor in HCC. Our research identified two RNA modification patterns characterized by distinct TME, and the WM-Score model was developed that might serve as reliable prognostic and immunotherapeutic effect predictor of HCC.
RNA修饰已成为多种肿瘤细胞过程和肿瘤发生（包括肝细胞癌（HCC））中重要的转录后变化。然而，在HCC中，RNA修饰调节因子与肿瘤微环境（TME）之间的潜在作用及相互作用尚不清楚。在TCGA队列中研究了26种RNA修饰“书写者”的基因表达谱。采用无监督聚类方法对这些RNA修饰调节因子进行分类。通过CIBERSORT方法测试每个聚类中来自TME的免疫细胞浸润特征。此外，我们建立了一个评分模型来评估个体肿瘤的RNA修饰特征。还分析了评分模型与基因以及临床特征、药物敏感性和免疫治疗反应之间的关联。我们绘制了RNA修饰调节因子的体细胞突变和体细胞拷贝数变异图谱。检测了所有选定调节因子的表达，并确定了两种具有不同免疫细胞浸润特征的修饰模式。随后，我们开发了一个评分模型（称为WM-Score模型）。此外，生存分析表明WM-Score值与HCC患者预后相关。ROC曲线分析和多变量分析结果均证实WM-Score值与抗癌药物耐药性和免疫治疗疗效密切相关，因此可作为HCC的独立危险因素。我们的研究确定了两种以不同TME为特征的RNA修饰模式，并开发了WM-Score模型，该模型可能作为HCC可靠的预后和免疫治疗效果预测指标。
