鉴定一个新的 10 个免疫相关基因特征作为胃癌的预后生物标志物panel。
Identification of a novel 10 immune-related genes signature as a prognostic biomarker panel for gastric cancer.
机构信息
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.
出版信息
Cancer Med. 2021 Sep;10(18):6546-6560. doi: 10.1002/cam4.4180. Epub 2021 Aug 12.
BACKGROUND
Emerging evidence indicates that immune infiltrating cells in tumor microenvironment (TME) correlates with the development and progression of gastric cancer (GC). This study aimed to systematically investigate the immune-related genes (IRGs) to develop a prognostic signature to predict the overall survival (OS) in GC.
METHOD
The gene expression profiles of training dataset (GSE62254), validation dataset I (GSE15459), and validation dataset II (GSE84437) were retrieved from GEO and TCGA databases. In the present study, we developed a 10 IRGs prognostic signature with the combination of weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator method (LASSO) COX model.
RESULTS
In the training dataset, the accuracy of the signature was 0.681, 0.741, and 0.72 in predicting 1, 3, and 5-year OS separately. The signature also had good performance in validation dataset Ⅰ with the accuracy of 0.57, 0.619, and 0.694, and in validation dataset Ⅱ with the accuracy of 0.559, 0.624, and 0.585. Then, we constructed a nomogram using the signature and clinical information which had strong discrimination ability with the c-index of 0.756. In the immune infiltration analysis, the signature was correlated with multiple immune infiltrating cells such as CD8 T cells, CD4 memory T cells, NK cells, and macrophages. Furthermore, several significant pathways were enriched in gene set enrichment analysis (GSEA) analysis, including TGF-beta signaling pathway and Wnt signaling pathway.
CONCLUSION
The signature of 10 IRGs we identified can effectively predict the prognosis of GC and provides new insight into discovering candidate prognostic biomarkers of GC.
背景
新兴证据表明,肿瘤微环境(TME)中的免疫浸润细胞与胃癌(GC)的发生和发展相关。本研究旨在系统研究免疫相关基因(IRGs),以开发一种预测 GC 总生存期(OS)的预后签名。
方法
从 GEO 和 TCGA 数据库中检索了训练数据集(GSE62254)、验证数据集 I(GSE15459)和验证数据集 II(GSE84437)的基因表达谱。在本研究中,我们结合加权基因共表达网络分析(WGCNA)和最小绝对收缩和选择算子方法(LASSO) COX 模型,开发了一个 10 个 IRGs 预后签名。
结果
在训练数据集中,该签名分别在预测 1、3 和 5 年 OS 时的准确率为 0.681、0.741 和 0.72。该签名在验证数据集 Ⅰ中的准确率为 0.57、0.619 和 0.694,在验证数据集 Ⅱ中的准确率为 0.559、0.624 和 0.585,表现良好。然后,我们使用该签名和临床信息构建了一个列线图,其 C 指数为 0.756,具有较强的区分能力。在免疫浸润分析中,该签名与多种免疫浸润细胞相关,如 CD8+T 细胞、CD4+记忆 T 细胞、NK 细胞和巨噬细胞。此外,基因集富集分析(GSEA)分析中富集了几个显著通路,包括 TGF-β信号通路和 Wnt 信号通路。
结论
我们确定的 10 个 IRGs 签名可以有效地预测 GC 的预后,并为发现 GC 的候选预后生物标志物提供了新的见解。