Wang Yanbo, Liu Jing, Ren Fenghai, Chu Yanjie, Cui Binbin
Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Genet. 2021 Jul 5;12:671128. doi: 10.3389/fgene.2021.671128. eCollection 2021.
The emerging evidence has demonstrated the critical roles of long non-coding RNAs (lncRNAs) as regulators in the tumor immune microenvironment (TIME). However, the tumor immune infiltration-associated lncRNAs and their clinical significance in colon cancer have not yet been thoroughly investigated. This study performed an integrative analysis of lncRNA expression profiles and immune cell infiltration profiles and identified 258 immune infiltration-associated lncRNAs. Of them, four lncRNAs (AC008494.3, LINC00926, AC022034.1, and SNHG26) were significantly and independently associated with the patient's overall survival. Finally, we developed a tumor immune infiltration-associated lncRNA signature (TIILncSig) comprising of these four lncRNAs, which can divide colon cancer patients of The Cancer Genome Atlas (TCGA) into high-risk and low-risk groups with a significantly different outcome [Hazard ratio (HR) = 2.718, 95% CI = 1.955-3.779, < 0.001]. Prognostic performance of the TIILncSig was further validated in another independent colon cancer cohort (HR = 1.832, 95% CI = 1.045-3.21, = 0.034). Results of multivariate Cox regression and stratification analysis demonstrated that the TIILncSig is an independent predictive factor from other clinical features (HR = 2.687, 95% CI = 1.912-3.776, < 0.001 for TCGA cohort and HR = 1.837, 95% CI = 1.047-3.223, = 0.034 for GSE17538 cohort). Literature analysis provided experimental evidence supporting roles of the TIILncSig in cancer carcinogenesis and progression and immune regulation. Summary, our study will help to understand the mechanisms of lncRNAs in immune regulation in the tumor microenvironment and provide novel biomarkers or targets for prognosis prediction and therapy decision-making for patients with colon cancer.
新出现的证据表明，长链非编码RNA（lncRNA）作为肿瘤免疫微环境（TIME）中的调节因子发挥着关键作用。然而，与肿瘤免疫浸润相关的lncRNA及其在结肠癌中的临床意义尚未得到充分研究。本研究对lncRNA表达谱和免疫细胞浸润谱进行了综合分析，鉴定出258个与免疫浸润相关的lncRNA。其中，4个lncRNA（AC008494.3、LINC00926、AC022034.1和SNHG26）与患者的总生存期显著且独立相关。最后，我们开发了一种由这4个lncRNA组成的肿瘤免疫浸润相关lncRNA特征（TIILncSig），它可以将癌症基因组图谱（TCGA）的结肠癌患者分为高风险和低风险组，两组的预后有显著差异[风险比（HR）=2.718，95%置信区间（CI）=1.955 - 3.779，P<0.001]。TIILncSig的预后性能在另一个独立的结肠癌队列中得到了进一步验证（HR = 1.832，95% CI = 1.045 - 3.21，P = 0.034）。多变量Cox回归和分层分析结果表明，TIILncSig是一个独立于其他临床特征的预测因子（TCGA队列中HR = 2.687，95% CI = 1.912 - 3.776，P<0.001；GSE17538队列中HR = 1.837，95% CI = 1.047 - 3.223，P = 0.034）。文献分析提供了实验证据，支持TIILncSig在癌症发生、发展和免疫调节中的作用。总之，我们的研究将有助于理解lncRNA在肿瘤微环境免疫调节中的机制，并为结肠癌患者的预后预测和治疗决策提供新的生物标志物或靶点。
