Wu Guomin, Wang Qihao, Zhu Ting, Fu Linhai, Li Zhupeng, Wu Yuanlin, Zhang Chu
School of Medicine, Shaoxing University, Shaoxing, China.
Department of Thoracic Surgery, Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, China.
Front Genet. 2021 Jul 5;12:681277. doi: 10.3389/fgene.2021.681277. eCollection 2021.
This study aimed to establish a prognostic risk model for lung adenocarcinoma (LUAD). We firstly divided 535 LUAD samples in TCGA-LUAD into high-, medium-, and low-immune infiltration groups by consensus clustering analysis according to immunological competence assessment by single-sample gene set enrichment analysis (ssGSEA). Profile of long non-coding RNAs (lncRNAs) in normal samples and LUAD samples in TCGA was used for a differential expression analysis in the high- and low-immune infiltration groups. A total of 1,570 immune-related differential lncRNAs in LUAD were obtained by intersecting the above results. Afterward, univariate COX regression analysis and multivariate stepwise COX regression analysis were conducted to screen prognosis-related lncRNAs, and an eight-immune-related-lncRNA prognostic signature was finally acquired (AL365181.2, AC012213.4, DRAIC, MRGPRG-AS1, AP002478.1, AC092168.2, FAM30A, and LINC02412). Kaplan-Meier analysis and ROC analysis indicated that the eight-lncRNA-based model was accurate to predict the prognosis of LUAD patients. Simultaneously, univariate COX regression analysis and multivariate COX regression analysis were undertaken on clinical features and risk scores. It was illustrated that the risk score was a prognostic factor independent from clinical features. Moreover, immune data of LUAD in the TIMER database were analyzed. The eight-immune-related-lncRNA prognostic signature was related to the infiltration of B cells, CD4+ T cells, and dendritic cells. GSEA enrichment analysis revealed significant differences in high- and low-risk groups in pathways like pentose phosphate pathway, ubiquitin mediated proteolysis, and P53 signaling pathway. This study helps to treat LUAD patients and explore molecules related to LUAD immune infiltration to deeply understand the specific mechanism.
本研究旨在建立肺腺癌(LUAD)的预后风险模型。我们首先根据单样本基因集富集分析(ssGSEA)进行免疫能力评估,通过共识聚类分析将TCGA-LUAD中的535个LUAD样本分为高、中、低免疫浸润组。利用TCGA中正常样本和LUAD样本的长链非编码RNA(lncRNA)谱在高、低免疫浸润组中进行差异表达分析。通过上述结果的交集,共获得1570个LUAD中与免疫相关的差异lncRNA。随后,进行单因素COX回归分析和多因素逐步COX回归分析以筛选与预后相关的lncRNA,最终获得了一个由八个与免疫相关的lncRNA组成的预后特征(AL365181.2、AC012213.4、DRAIC、MRGPRG-AS1、AP002478.1、AC092168.2、FAM30A和LINC02412)。Kaplan-Meier分析和ROC分析表明,基于八个lncRNA的模型能够准确预测LUAD患者的预后。同时,对临床特征和风险评分进行了单因素COX回归分析和多因素COX回归分析。结果表明,风险评分是一个独立于临床特征的预后因素。此外,还分析了TIMER数据库中LUAD的免疫数据。这八个与免疫相关的lncRNA预后特征与B细胞、CD4+T细胞和树突状细胞的浸润有关。GSEA富集分析显示,高、低风险组在磷酸戊糖途径、泛素介导的蛋白水解和P53信号通路等途径上存在显著差异。本研究有助于治疗LUAD患者,并探索与LUAD免疫浸润相关的分子,以深入了解其具体机制。