Chai Xiu-Kun, Qi Wei, Zou Chun-Yan, He Chen-Xi, Su Miao, Zhao Dong-Qiang
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Gastroenterology, Qinhuagdao First Hospital, Qinhuangdao, China.
Front Genet. 2021 Dec 22;12:774010. doi: 10.3389/fgene.2021.774010. eCollection 2021.
Long non-coding RNAs (lncRNAs) and their N6-methyladenosine (m6A) modifications play an essential role in tumorigenesis and cancer progression. This study was designed to explore the value of m6A-related lncRNAs in prognosis and therapeutic applications of immune infiltration of colon adenocarcinoma (COAD). We downloaded the COAD gene expression and clinical data from The Cancer Genome Atlas project. By co-expression analysis, Lasso Cox regression analysis, and univariate and multivariate Cox regression, we constructed an independent prognostic signature of seven m6A-related lncRNAs. The prognostic lncRNAs were divided into two clusters by consistent clustering analysis, as well as into two groups of low-high risk based on the signature. Then we identified the relationship between the different groups with clinical features and immune cell infiltration. Cluster 2 had a higher risk score with a lower survival rate. The risk score was higher in groups with advanced clinical features, such as stage III-IV, N1-3, and M1. The expression of AC156455.1 was increased in tumor tissues and cluster 2, and the lncRNA ZEB1-AS1 was notably higher in the high-risk group. Five types of immune cells showed differences in two clusters, and most were upregulated in type 2. The expression of memory B cells was positively correlated with the risk score. The prognostic model was verified by the Gene Expression Omnibus (GEO) dataset. Besides, we found that the expression of these seven lncRNAs in tumor tissues was significantly higher than that in normal tissues, which verified the feasibility of the model. Thus, the signature of seven m6A-related lncRNAs can independently predict the prognosis of COAD. This signature is also closely associated with immune cell infiltration, and new therapeutic targets can be explored from this field.
长链非编码RNA(lncRNAs)及其N6-甲基腺苷(m6A)修饰在肿瘤发生和癌症进展中起着至关重要的作用。本研究旨在探讨m6A相关lncRNAs在结肠腺癌(COAD)免疫浸润的预后和治疗应用中的价值。我们从癌症基因组图谱项目下载了COAD基因表达和临床数据。通过共表达分析、套索Cox回归分析以及单变量和多变量Cox回归,我们构建了一个由7个m6A相关lncRNAs组成的独立预后特征。通过一致性聚类分析将预后lncRNAs分为两个簇,并根据该特征分为低风险和高风险两组。然后我们确定了不同组与临床特征和免疫细胞浸润之间的关系。簇2具有较高的风险评分和较低的生存率。在具有晚期临床特征的组中,如III-IV期、N1-3和M1,风险评分较高。AC156455.1在肿瘤组织和簇2中的表达增加,lncRNA ZEB1-AS1在高风险组中显著更高。五种免疫细胞在两个簇中表现出差异,大多数在簇2中上调。记忆B细胞的表达与风险评分呈正相关。通过基因表达综合数据库(GEO)数据集验证了预后模型。此外,我们发现这7个lncRNAs在肿瘤组织中的表达显著高于正常组织中,这验证了该模型的可行性。因此,7个m6A相关lncRNAs的特征可以独立预测COAD的预后。该特征也与免疫细胞浸润密切相关,可以从该领域探索新的治疗靶点。