Wang Haixu, Meng Qingkai, Ma Bin
Postgraduate Training Base in General Hospital of The Northern Theater Command, China Medical University, Shenyang, China.
Department of Radiation Oncology, The General Hospital of Northern Theater Command, Shenyang, China.
Front Oncol. 2021 Apr 13;11:630260. doi: 10.3389/fonc.2021.630260. eCollection 2021.
N6-methyladenosine (mA) is a common form of mRNA modification regulated by m6A RNA methylation regulators and play an important role in the progression of gastric cancer (GC). However, the prognostic role of mA-related lncRNA in gastric cancer has not been fully explored. This study aims at exploring the biological function and prognostic roles of the mA-related lncRNA signature in gastric cancer. A total of 800 m6A-related lncRNAs were identified through Pearson correlation analysis between m6A regulators and all lncRNAs. Eleven m6A-related lncRNA signatures were identified through a survival analysis and the Kaplan-Meier (KM) curve analysis results suggest that patients in the low-risk group have a better overall survival (OS) and disease-free survival (DFS) outcome than the high-risk group. Also, the lncRNA signature can serve as an independent prognostic factor for OS and DFS. The gene set enrichment analysis (GSEA) result suggests that patients in the high-risk group were mainly enriched in the ECM receptor interaction, focal adhesion, and cytokine-cytokine receptor interaction pathway, while the low-risk group was characterized by the base excision repair pathway. We further constructed an individualized prognostic prediction model the nomogram based on the independent prognostic factor for the OS and DFS, respectively. In addition, some candidate drugs aimed at GC risk group differentiation were identified using the Connective Map (CMAP) database. Lastly, four subgroups (C1, C2, C3, and C4) were identified based on the m6A-related lncRNA expression, through a consensus clustering algorithm. Among them, C1 and C2 have a greater likelihood to respond to immune checkpoint inhibitor immunotherapy, suggesting that the C1 and C2 subgroup might benefit from immunotherapy. In conclusion, the m6A-related lncRNA signature can independently predict the OS and DFS of GC and may aid in development of personalized immunotherapy strategies.
N6-甲基腺苷(mA)是一种常见的mRNA修饰形式,受m6A RNA甲基化调节因子调控,在胃癌(GC)进展中起重要作用。然而,与mA相关的长链非编码RNA(lncRNA)在胃癌中的预后作用尚未得到充分研究。本研究旨在探讨与mA相关的lncRNA特征在胃癌中的生物学功能和预后作用。通过对m6A调节因子与所有lncRNA进行Pearson相关性分析,共鉴定出800个与m6A相关的lncRNA。通过生存分析鉴定出11个与m6A相关的lncRNA特征,Kaplan-Meier(KM)曲线分析结果表明,低风险组患者的总生存期(OS)和无病生存期(DFS)结果优于高风险组。此外,lncRNA特征可作为OS和DFS的独立预后因素。基因集富集分析(GSEA)结果表明,高风险组患者主要富集于细胞外基质受体相互作用、粘着斑和细胞因子-细胞因子受体相互作用途径,而低风险组的特征是碱基切除修复途径。我们分别基于OS和DFS的独立预后因素进一步构建了个性化预后预测模型——列线图。此外,利用连接图谱(CMAP)数据库鉴定了一些针对GC风险组分化的候选药物。最后,通过一致性聚类算法,基于与m6A相关的lncRNA表达鉴定出四个亚组(C1、C2、C3和C4)。其中,C1和C2对免疫检查点抑制剂免疫治疗有更大的反应可能性,表明C1和C2亚组可能从免疫治疗中获益。总之,与m6A相关的lncRNA特征可独立预测GC的OS和DFS,并可能有助于制定个性化免疫治疗策略。