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一种新型的 10 基因免疫相关长链非编码 RNA 签名模型,用于预测结直肠癌的预后。

A novel 10-gene immune-related lncRNA signature model for the prognosis of colorectal cancer.

机构信息

Department of Colorectal Surgery, Liaoning Cancer Hospital & Institute (Cancer Hospital of China Medical University), Shenyang, China.

出版信息

Math Biosci Eng. 2021 Nov 4;18(6):9743-9760. doi: 10.3934/mbe.2021477.

DOI:10.3934/mbe.2021477
PMID:34814366
Abstract

BACKGROUND

The tumor immune microenvironment of colorectal cancer (CRC) affects tumor development, prognosis and immunotherapy strategies. Recently, immune-related lncRNA were shown to play vital roles in the tumor immune microenvironment. The objective of this study was to identify lncRNAs involved in the immune response, tumorigenesis and progression of CRC and to establish an immune-related lncRNA signature for predicting the prognosis of CRC.

METHODS

We used data retrieved from the cancer genome atlas (TCGA) dataset to construct a 10-gene immune-related lncRNA pair (IRLP) signature model using a method based on the ranking and comparison of paired gene expression in CRC. The clinical prognosis, immune checkpoints and lncRNA-protein networks were analyzed to evaluate the signature.

RESULTS

The signature was closely associated with overall survival of CRC patients (p < 0.001 in both of the training and validating cohorts) and the 3-year AUC values for the training and validating cohorts were 0.884 and 0.739, respectively. And, there were positive correlations between the signature and age (p = 0.048), clinical stage (p < 0.01), T stage (p < 0.01), N stage (p < 0.001) and M stage (p < 0.01). In addition, the signature model appeared to be highly relevant to some checkpoints, including CD160, TNFSF15, HHLA2, IDO2 and KIR3DL1. Further, molecular functional analysis and lncRNA-protein networks were applied to understand the molecular mechanisms underlying the carcinogenic effect and progression.

CONCLUSION

The 10-gene IRLP signature model is an independent prognostic factor for CRC patient and can be utilized for the development of immunotherapy.

摘要

背景

结直肠癌(CRC)的肿瘤免疫微环境影响肿瘤的发展、预后和免疫治疗策略。最近,免疫相关长链非编码 RNA(lncRNA)被证明在肿瘤免疫微环境中发挥着重要作用。本研究旨在鉴定参与 CRC 免疫反应、肿瘤发生和进展的 lncRNA,并建立免疫相关 lncRNA 特征来预测 CRC 的预后。

方法

我们使用从癌症基因组图谱(TCGA)数据库中检索到的数据,使用基于 CRC 中配对基因表达排序和比较的方法,构建了一个由 10 个基因组成的免疫相关 lncRNA 对(IRLP)特征模型。分析了特征的临床预后、免疫检查点和 lncRNA-蛋白网络。

结果

该特征与 CRC 患者的总生存期密切相关(在训练和验证队列中均为 p<0.001),训练和验证队列的 3 年 AUC 值分别为 0.884 和 0.739。此外,特征与年龄(p=0.048)、临床分期(p<0.01)、T 分期(p<0.01)、N 分期(p<0.001)和 M 分期(p<0.01)呈正相关。此外,该特征模型似乎与一些检查点高度相关,包括 CD160、TNFSF15、HHLA2、IDO2 和 KIR3DL1。此外,进行了分子功能分析和 lncRNA-蛋白网络分析,以了解致癌作用和进展的分子机制。

结论

该 10 个基因的 IRLP 特征模型是 CRC 患者的独立预后因素,可用于免疫治疗的开发。

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