Song Wei, Ren Jun, Wang Chuntao, Ge Yuhang, Fu Tao
Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, China.
Front Genet. 2020 Jun 3;11:505. doi: 10.3389/fgene.2020.00505. eCollection 2020.
Recent papers have described circular RNAs (circRNAs) playing important roles in the development and progression of colorectal cancer (CRC). However, the expression profiles of circRNAs and their functions in CRC have rarely been studied. The objective was to identify circRNAs involved in the carcinogenesis and progression of CRC and to explore potential molecular mechanisms as a competitive endogenous RNA (ceRNA). Moreover, we aimed to establish an immune-related gene signature for predicting the overall survival (OS) of CRC.
The expression patterns of circRNA, miRNA, mRNA, and clinicopathological data were collected from the GEO and TCGA databases. A ceRNA network would be established, and the functional enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed, and hub genes were identified using a cytohub plugin. Subsequently, an immune-related signature was developed based on mRNAs in the ceRNA network. In addition, OS-nomogram was constructed by combining an immune-related signature and clinicopathological characterization to predict the OS.
We established a circRNA-miRNA-mRNA ceRNA network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the mRNAs were mainly enriched in neuroactive ligand-receptor interaction, Wnt signaling pathway, cell adhesion molecules (CAMs), and renin secretion. PPI network and module analysis identified 10 hub genes, and the circRNA-miRNA hub gene regulatory modules was established. After univariate and multivariate analysis, seven immune-related genes in the ceRNA network were used to construct the immune-related signature. Patients were divided into low-risk and high-risk groups, and there were significant differences in the OS. The ROC of the nomogram indicated the satisfactory accuracy and predictive power. Furthermore, we established a prognostic nomogram based on immune-related risk score and clinical characterization. The ROC and calibration curves revealed the accuracy of the nomogram. In addition, the high-risk score was positively correlated with six immune infiltrating cells ( < 0.05).
We screened the key genes and established a circRNA-related ceRNA network involved in CRC, which will assist in understanding the molecular mechanisms underlying the carcinogenesis and progression. Moreover, our proposed immune-based signature may predict survival and reflect the immune status of CRC patients.
近期的论文描述了环状RNA（circRNA）在结直肠癌（CRC）的发生和发展中发挥重要作用。然而，circRNA在CRC中的表达谱及其功能鲜有研究。目的是鉴定参与CRC致癌作用和进展的circRNA，并探索作为竞争性内源性RNA（ceRNA）的潜在分子机制。此外，我们旨在建立一种免疫相关基因特征来预测CRC的总生存期（OS）。
从GEO和TCGA数据库收集circRNA、miRNA、mRNA的表达模式及临床病理数据。构建ceRNA网络，并进行功能富集分析。构建蛋白质-蛋白质相互作用网络（PPI），使用cytohub插件鉴定枢纽基因。随后，基于ceRNA网络中的mRNA开发免疫相关特征。此外，通过结合免疫相关特征和临床病理特征构建OS列线图以预测OS。
我们建立了一个circRNA-miRNA-mRNA ceRNA网络。京都基因与基因组百科全书（KEGG）通路分析显示，mRNA主要富集于神经活性配体-受体相互作用、Wnt信号通路、细胞黏附分子（CAMs）和肾素分泌。PPI网络和模块分析鉴定出10个枢纽基因，并建立了circRNA-miRNA枢纽基因调控模块。经过单因素和多因素分析，ceRNA网络中的7个免疫相关基因用于构建免疫相关特征。患者分为低风险和高风险组，OS存在显著差异。列线图的ROC显示出令人满意的准确性和预测能力。此外，我们基于免疫相关风险评分和临床特征建立了一个预后列线图。ROC和校准曲线显示了列线图的准确性。此外，高风险评分与六种免疫浸润细胞呈正相关（<0.05）。
我们筛选出关键基因并建立了一个与CRC相关的circRNA ceRNA网络，这将有助于理解致癌作用和进展的潜在分子机制。此外，我们提出的基于免疫的特征可能预测生存期并反映CRC患者的免疫状态。
