A signature of seven immune-related genes predicts overall survival in male gastric cancer patients.
A signature of seven immune-related genes predicts overall survival in male gastric cancer patients.
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DOI：
10.1186/s12935-021-01823-0
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发表时间：
2021-02-18
影响因子：
5.8
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Xu X;Lu Y;Wu Y;Wang M;Wang X;Wang H;Chen B;Li Y
胃癌（GC）死亡率很高，是最致命的恶性肿瘤之一。男性已被证明是胃癌的独立危险因素。本研究旨在鉴定与男性 GC 预后相关的免疫相关基因 (IRG)。 RNA 测序和临床数据来自癌症基因组图谱 (TCGA) 数据库。通过综合生物信息学分析鉴定了男性GC和正常组织之间差异表达的IRG。应用单变量和多变量 Cox 回归分析来筛选与生存相关的 IRG。然后，根据中位风险评分将GC患者分为高风险组和低风险组。此外，基于 TCGA 数据集构建了列线图。通过Kaplan-Meier曲线、受试者工作特征（ROC）、Harrell一致性指数和校准曲线评估风险特征模型的预后价值。此外，还下载了基因表达综合库（GEO）的基因表达数据集以进行外部验证。使用 CIBERSORT 评估每个男性 GC 样本中 22 种浸润免疫细胞的相对比例。 共筛选出276个差异表达的IRG，其中上调基因189个，下调基因87个。随后，七种 IRG 特征（LCN12、CCL21、RNASE2、CGB5、NRG4、AGTR1 和 NPR3）被确定与男性 GC 患者的总生存期 (OS) 显着相关。生存分析表明高危组患者的临床结果较差。多变量分析结果显示，风险评分是一个独立的预后因素。建立的列线图可用于评估个体男性GC患者的预后。进一步分析表明，该预后模型在 TCGA 和验证队列中均具有出色的预测性能。此外，肿瘤浸润免疫细胞分析结果表明，七-IRGs特征可以反映肿瘤免疫微环境的状态。我们的研究开发了一种新的 7-IRG 风险特征，用于男性 GC 患者的个体化生存预测。
Gastric cancer (GC) has a high mortality rate and is one of the most fatal malignant tumours. Male sex has been proven as an independent risk factor for GC. This study aimed to identify immune-related genes (IRGs) associated with the prognosis of male GC. RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs between male GC and normal tissues were identified by integrated bioinformatics analysis. Univariate and multivariate Cox regression analyses were applied to screen survival-associated IRGs. Then, GC patients were separated into high- and low-risk groups based on the median risk score. Furthermore, a nomogram was constructed based on the TCGA dataset. The prognostic value of the risk signature model was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell’s concordance index and calibration curves. In addition, the gene expression dataset from the Gene Expression Omnibus (GEO) was also downloaded for external validation. The relative proportions of 22 types of infiltrating immune cells in each male GC sample were evaluated using CIBERSORT. A total of 276 differentially expressed IRGs were screened, including 189 up-regulated and 87 down-regulated genes. Subsequently, a seven-IRGs signature (LCN12, CCL21, RNASE2, CGB5, NRG4, AGTR1 and NPR3) was identified to be significantly associated with the overall survival (OS) of male GC patients. Survival analysis indicated that patients in the high-risk group exhibited a poor clinical outcome. The results of multivariate analysis revealed that the risk score was an independent prognostic factor. The established nomogram could be used to evaluate the prognosis of individual male GC patients. Further analysis showed that the prognostic model had excellent predictive performance in both TCGA and validated cohorts. Besides, the results of tumour-infiltrating immune cell analysis indicated that the seven-IRGs signature could reflect the status of the tumour immune microenvironment. Our study developed a novel seven-IRGs risk signature for individualized survival prediction of male GC patients.
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