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一种预测结肠癌总生存期的免疫相关九lncRNA特征的鉴定

Identification of an Immune-Related Nine-lncRNA Signature Predictive of Overall Survival in Colon Cancer.

作者信息

Lin Yilin, Pan Xiaoxian, Chen Zhihua, Lin Suyong, Chen Shaoqin

机构信息

Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Department of Radiotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

出版信息

Front Genet. 2020 Apr 30;11:318. doi: 10.3389/fgene.2020.00318. eCollection 2020.

Abstract

Growing evidence suggests that immune-related genes (IRGs) and long non-coding RNAs (lncRNAs) can serve as prognostic markers of overall survival (OS) in patients with colon cancer. This study aimed to identify an immune-related lncRNA signature for the prospective assessment of prognosis in these patients. Gene expression and clinical data of colon cancer patients were downloaded from The Cancer Genome Atlas (TCGA). Immune-related lncRNAs were identified by a correlation analysis between IRGs and lncRNAs. In total, 447 samples were divided into a training cohort (224 samples) and a testing cohort (223 samples). Univariate, lasso and multivariate Cox regression analyses identified an immune-related nine-lncRNA signature closely related to OS in colon cancer patients in the training dataset. A risk score formula involving nine immune-related lncRNAs was developed to evaluate the prognostic value of the lncRNA signature in the training dataset. Colon cancer patients with a high risk score had poorer OS than those with a low risk score. A multivariate Cox regression analysis confirmed that the immune-related nine-lncRNA signature could be an independent prognostic factor in colon cancer patients. The results were further confirmed in the testing cohort and the entire TCGA cohort. Furthermore, a gene set enrichment analysis revealed several pathways with significant enrichment in the high- and low-risk groups that may be helpful in formulating clinical strategies and understanding the underlying mechanisms. Finally, a quantitative real-time polymerase chain reaction assay found that the nine lncRNAs were significantly differentially expressed in colon cancer cell lines. The results of this study indicate that this signature has important clinical implications for improving predictive outcomes and guiding individualized treatment in colon cancer patients. These lncRNAs could be potential biomarkers affecting the prognosis of colon cancer.

摘要

越来越多的证据表明,免疫相关基因(IRGs)和长链非编码RNA(lncRNAs)可作为结肠癌患者总生存期(OS)的预后标志物。本研究旨在识别一种免疫相关lncRNA特征,用于前瞻性评估这些患者的预后。从癌症基因组图谱(TCGA)下载了结肠癌患者的基因表达和临床数据。通过IRGs与lncRNAs之间的相关性分析鉴定出免疫相关lncRNAs。总共447个样本被分为训练队列(224个样本)和测试队列(223个样本)。单因素、套索和多因素Cox回归分析在训练数据集中确定了一种与结肠癌患者OS密切相关的免疫相关九lncRNA特征。开发了一个涉及9种免疫相关lncRNAs的风险评分公式,以评估lncRNA特征在训练数据集中的预后价值。高风险评分的结肠癌患者的OS比低风险评分的患者差。多因素Cox回归分析证实,免疫相关九lncRNA特征可能是结肠癌患者的独立预后因素。在测试队列和整个TCGA队列中进一步证实了结果。此外,基因集富集分析揭示了高风险和低风险组中显著富集的几种途径,这可能有助于制定临床策略和理解潜在机制。最后,定量实时聚合酶链反应分析发现这9种lncRNAs在结肠癌细胞系中显著差异表达。本研究结果表明,该特征对改善结肠癌患者的预测结果和指导个体化治疗具有重要临床意义。这些lncRNAs可能是影响结肠癌预后的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d971/7203495/f16e8b23059c/fgene-11-00318-g001.jpg

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