A robust immune-related lncRNA signature for the prognosis of human colorectal cancer.
A robust immune-related lncRNA signature for the prognosis of human colorectal cancer.
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DOI：
10.1042/bsr20220078
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发表时间：
2022-07-29
影响因子：
4
通讯作者：
Zhang, Chenliang
中科院分区：
文献类型：
--
作者：
Zhu, Gongmin;Pei, Lijiao;Yang, Fan;Zhang, Chenliang
背景：结直肠癌（Colorectal cancer， CRC）是全球最常见的恶性肿瘤之一。免疫相关的长链非编码rna （IRlncRNAs）在癌症的发生和发展中被证明是必不可少的。本研究的目的是开发和验证CRC患者预后的IRlncRNA标记。方法：从癌症基因组图谱（TCGA）数据库下载结直肠癌样本的基因表达谱。从import数据库中获取免疫相关基因，通过相关分析鉴定IRlncRNA。通过LASSO - Cox回归分析，构建预后特征。功能富集分析采用基因集富集分析（GSEA）。采用TIMER2.0 web服务器和肿瘤免疫功能障碍与排斥（tumor immune dysfunction and exclusion， TIDE）算法分析我们的模型与肿瘤浸润性免疫细胞和免疫治疗应答的关系。采用实时荧光定量PCR （quantitative real-time PCR, qPCR）检测IRlncRNAs在细胞系中的表达水平。结果：通过LASSO Cox比例回归模型建立了9-IRlncRNA特征。根据签名将结直肠癌患者分为不同预后的高危组和低危组。GSEA结果提示高危组患者存在肿瘤相关通路。此外，低危组患者抗肿瘤免疫细胞浸润更多，可能对免疫治疗有较好的反应。最后，qPCR结果显示，大多数irlncrna在正常细胞系和肿瘤细胞系之间表达不同。结论：构建的9-IRlncRNA信号具有预测结直肠癌患者预后的潜力，可能有助于指导个体化免疫治疗。
Background: Colorectal cancer (CRC) is one of the most prevalent malignant cancers worldwide. Immune-related long non-coding RNAs (IRlncRNAs) are proved to be essential in the development and progression of carcinoma. The purpose of the present study was to develop and validate a prognostic IRlncRNA signature for CRC patients. Methods: Gene expression profiles of CRC samples were downloaded from The Cancer Genome Atlas (TCGA) database. Immune-related genes were obtained from the ImmPort database and were used to identify IRlncRNA by correlation analysis. Through LASSO Cox regression analyses, a prognostic signature was constructed. Functional enrichment analysis was performed by gene set enrichment analysis (GSEA). TIMER2.0 web server and tumor immune dysfunction and exclusion (TIDE) algorithm were employed to analyze the association between our model and tumor-infiltrating immune cells and immunotherapy response. The expression levels of IRlncRNAs in cell lines were detected by quantitative real-time PCR (qPCR). Results: A 9-IRlncRNA signature was developed by a LASSO Cox proportional regression model. Based on the signature, CRC patients were divided into high- and low-risk groups with different prognoses. GSEA results indicated that patients in high-risk group were associated with cancer-related pathways. In addition, patients in low-risk group were found to have more infiltration of anti-tumor immune cells and might show a favorable response to immunotherapy. Finally, the result of qPCR revealed that most IRlncRNAs were differently expressed between normal and tumor cell lines. Conclusion: The constructed 9-IRlncRNA signature has potential to predict the prognosis of CRC patients and may be helpful to guide personalized immunotherapy.