Comprehensive Analysis and Prognosis Prediction of N6-Methyladenosine-Related lncRNAs in Immune Microenvironment Infiltration of Gastric Cancer.
Comprehensive Analysis and Prognosis Prediction of N6-Methyladenosine-Related lncRNAs in Immune Microenvironment Infiltration of Gastric Cancer.
复制标题
在免疫微环境渗透胃癌中，N6-甲基腺苷相关的LNCRNA的综合分析和预测预测。
DOI：
10.2147/ijgm.s349399
复制
发表时间：
2022
影响因子：
2.3
通讯作者：
Xiao T
中科院分区：
文献类型：
--
作者：
Huang J;Chen W;Chen C;Jie Z;Xiao T
N6-甲基腺苷（m6 A）RNA修饰在调节肿瘤微环境（TME）浸润中起重要作用。然而，m6 A相关的长链非编码RNA（lncRNA）的表达模式与胃癌（GC）免疫微环境之间的关系尚不清楚。本研究通过Pearson相关分析和单变量考克斯回归分析鉴定了23个与m6 A相关的lncRNA。根据这些lncRNA的表达情况，我们通过一致性聚类将其分为两个不同的分子簇，并比较了两个分子簇在TME和富集途径上的差异。我们进一步构建了一个预后风险特征，并使用癌症基因组图谱训练和测试队列进行了验证。结果表明，簇1与肿瘤相关和免疫激活相关的通路相关。此外，聚类1还与较高的ImmuneScore、StromalScore和ESTIMATEScore相关。分层生存分析和独立预后分析的结果表明，风险信号是胃癌患者的独立预后指标。此外，它可以有效地预测不同临床特征患者的生存状况。此外，我们发现风险特征与各种肿瘤浸润免疫细胞相关，低风险评分与程序性死亡-1（PD-1）和细胞毒性T淋巴细胞相关蛋白4（CTLA 4）的高表达以及对化疗药物（如氟尿嘧啶和奥沙利铂）的敏感性显著相关。这一证据有助于我们理解m6 A相关lncRNA对TME浸润的调节，并可能为GC患者提供更有效的免疫治疗和化疗。
N6-methyladenosine (m6A) RNA modification plays an important role in regulating tumor microenvironment (TME) infiltration. However, the relationship between the expression pattern of m6A-related long non-coding RNAs (lncRNAs) and the immune microenvironment of gastric cancer (GC) is unclear. In this study, 23 m6A-related lncRNAs were identified by Pearson’s correlation analysis and univariate Cox regression analysis. According to the expression of these lncRNAs, we identified two distinct molecular clusters by consensus clustering and compared the differences of the TME and enriched pathways between the two clusters. We further constructed a prognostic risk signature and verified it using The Cancer Genome Atlas training and testing cohorts. The results showed that cluster 1 was associated with tumor-related and immune activation-related pathways. In addition, cluster 1 was also associated with higher ImmuneScore, StromalScore, and ESTIMATEScore. The results of the stratified survival analysis and independent prognosis analysis indicated that the risk signature is an independent prognostic indicator for patients with GC. In addition, it can effectively predict survival status in patients with different clinical characteristics. Furthermore, we found that the risk signature was associated with a variety of tumor-infiltrating immune cells, and that low risk scores were significantly correlated with high expression of programmed death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), as well as sensitivity to chemotherapeutic drugs (eg, fluorouracil and oxaliplatin). This evidence contributes to our understanding of the regulation of TME infiltration by m6A-related lncRNAs and may lead to more effective immunotherapy and chemotherapy for patients with GC.