← 返回

构建自噬相关的 11 个长链非编码 RNA 特征以预测胃癌患者的预后、免疫细胞浸润和免疫治疗反应

英文原题:Construction of an autophagy-related eleven long noncoding RNA signature to predict the outcomes, immune cell infiltration, and immunotherapy response in patients with gastric cancer.

查看英文原题

Construction of an autophagy-related eleven long noncoding RNA signature to predict the outcomes, immune cell infiltration, and immunotherapy response in patients with gastric cancer.

PubMed 2023/06/01(内容时间) J Physiol Pharmacol Q3 · IF 2.5(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

长链非编码RNA(LncRNA)可能通过调控自噬参与胃癌(GC)的发生、发展及耐药。本研究旨在建立自噬相关LncRNA(ARL)特征(ARLSig)并探讨其在GC患者中的免疫基因组学意义。从癌症基因组图谱数据库中提取GC患者的RNA测序和临床数据,从人类自噬数据库中提取自噬基因。进行共表达和Cox回归分析以建立预后ARLSig。

进一步,通过多种算法探讨风险组之间在临床病理学、免疫微环境、免疫功能及免疫治疗反应方面的差异。构建了由11个ARL组成的预后风险模型。ARLSig与临床病理因素的相关性分析表明,ARLSig与综合分期、T分期和N分期相关(均P<0.05)。

此外,包含ARLSig和临床因素的列线图提示其对生存具有强大的预测价值,对1年、3年和5年生存的预测效率高于其他临床病理因素。

最后,两个风险组之间的免疫相关分析显示,高风险组中静息NK 细胞、单核细胞、M2巨噬细胞和静息树突状细胞的浸润比例显著更高,以及25个免疫检查点基因的表达更高。

此外,通过分解算法追踪插入缺失的免疫治疗反应预测显示,低风险组对免疫检查点抑制剂治疗更敏感。GC中由11个ARL组成的ARLSig对GC患者的生存显示出高效预测价值,并可能为其个体化免疫治疗提供新靶点。

展开英文摘要原文

Long noncoding RNAs (LncRNAs) may be involved in the occurrence, development, and drug resistance of gastric cancer (GC) by regulating autophagy.

This study aims to establish an autophagy-related LncRNA (ARL) signature (ARLSig) and explore its immunogenomic implications in patients with GC. The RNA sequencing and clinical data of patients with GC from The Cancer Genome Atlas database, and autophagy genes from the Human Autophagy Database were extracted. The co-expression and Cox regression analyses were performed to establish a prognostic ARLSig.

Further, the differences in clinicopathology, immune microenvironment, immune function, and response to immunotherapy between the risk groups were explored by several algorithms. A prognostic risk model consisting of 11 ARLs was constructed. The clinical correlation analysis between the ARLSig and clinicopathological factors indicated that the ARLSig was correlated with the comprehensive, T, and N stages (all P<0. 05).

Further, a nomogram including the ARLSig and clinical factors suggested it had a powerful predictive value for survival, with a higher prediction efficiency for 1-, 3-, and 5-year survival than other clinicopathological factors.

Finally, the immune-related analysis between the two risk groups showed that the high-risk group had significantly higher infiltration proportions of natural killer cells resting, monocytes, M2 macrophages, and dendritic cells resting, as well as higher expression of 25 immune checkpoint genes.

In addition, the immunotherapy response prediction by the tracking of indels by decomposition algorithm showed the low-risk group was more sensitive to immune checkpoint inhibitor therapy. The ARLSig consisting of 11 ARLs in GC showed highly efficient predictive value for survival of patients with GC and might provide novel targets for their individualized immunotherapy.

论文信息

作者
Mu GC、Luo YJ、Chen JQ
第一作者单位
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, China.China
通讯作者单位
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, China. chenjunqiang@gxmu.edu.pl.China
期刊
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society2023 Jun
原文标识
PubMed 37661182 · DOI 10.26402/jpp.2023.3.05