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基于自噬相关长链非编码 RNA 的风险模型预测胃癌患者免疫治疗和化疗的预后和疗效。

A risk model based on autophagy-related lncRNAs for predicting prognosis and efficacy of immunotherapy and chemotherapy in gastric cancer patients.

机构信息

Department of Gastroenterology, The First Affiliated Hospital, And College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.

Department of Clinical Laboratory, The First Affiliated Hospital, And College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.

出版信息

Aging (Albany NY). 2021 Dec 12;13(23):25453-25465. doi: 10.18632/aging.203765.

Abstract

Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNAs essential to the occurrence and development of gastric cancer (GC). We aimed to identify critical lncRNA pairs to construct a prognostic model and assess its performances in prognosis and efficacy prediction in GC patients receiving immunotherapy and chemotherapy. We searched transcriptome and clinical data of GC patients from The Cancer Genome Atlas (TCGA) database. Autophagy-related lncRNAs were identified using co-expression network analysis, and lncRNA pairs with prognostic value were selected using pairwise transcriptome analysis. The gene pairs were subjected to LASSO algorithm for identification of optimal gene pairs for risk model construction. Patients were classified into the low-risk and high-risk groups with the RiskScore as a cutoff. Finally, 9 optimal gene pairs were identified in the LASSO algorithm model for construction of a lncRNA prognostic risk model. For predictive performances, it successfully predicted a shorter survival of high-risk patients than that obtained in low-risk individuals ( 0.001). It showed moderate AUC (area under the curve) values for 1-, 2-, and 3-year overall survival prediction of 0.713 and could serve as an independent predictor for GC prognosis. Compared to the low-risk group, high-risk patients had higher expressions of marker genes for immune checkpoint inhibitors (ICIs) and showed higher sensitivity to the chemotherapy agents, rapamycin, bexarotene, and bicalutamide. Our findings demonstrate a robust prognostic model based on nine autophagy-related lncRNA pairs for GC. It acts as an independent predictor for survival and efficacy prediction of immunotherapy and chemotherapy in GC patients.

摘要

长链非编码 RNA(lncRNA)是一类非蛋白编码 RNA,对胃癌(GC)的发生和发展至关重要。我们旨在鉴定关键的 lncRNA 对,构建一个预后模型,并评估其在接受免疫治疗和化疗的 GC 患者中的预后和疗效预测性能。我们从癌症基因组图谱(TCGA)数据库中搜索了 GC 患者的转录组和临床数据。使用共表达网络分析鉴定自噬相关 lncRNA,并使用成对转录组分析选择具有预后价值的 lncRNA 对。使用 LASSO 算法对基因对进行鉴定,以确定风险模型构建的最佳基因对。使用 RiskScore 作为截断值将患者分为低风险和高风险组。最后,在 LASSO 算法模型中鉴定了 9 个最佳基因对,用于构建 lncRNA 预后风险模型。对于预测性能,它成功预测了高风险患者的生存时间短于低风险个体( 0.001)。它对 1 年、2 年和 3 年总生存预测的 AUC(曲线下面积)值具有中等预测能力,可作为 GC 预后的独立预测因子。与低风险组相比,高风险患者的免疫检查点抑制剂(ICIs)标志物基因表达更高,对化疗药物雷帕霉素、贝沙罗汀和比卡鲁胺的敏感性更高。我们的研究结果表明,基于 9 个自噬相关 lncRNA 对的 GC 具有强大的预后模型。它是 GC 患者免疫治疗和化疗生存和疗效预测的独立预测因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faed/8714132/5c9ebdba4550/aging-13-203765-g001.jpg

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