A novel necroptosis-related gene index for predicting prognosis and a cold tumor immune microenvironment in stomach adenocarcinoma

作者：Muhammad Khan, Jie Lin, Baiyao Wang, Chengcong Chen, Zhong Huang, Yunhong Tian, Yawei Yuan, Junguo Bu · 发表于：Frontiers in Immunology · 年份：2022 · DOI：10.3389/fimmu.2022.968165 · 被引用次数：75 · 研究领域：Ferroptosis and cancer prognosis、Cell death mechanisms and regulation、Clusterin in disease pathology

Background Gastric cancer (GC) represents a major global clinical problem with very limited therapeutic options and poor prognosis. Necroptosis, a recently discovered inflammatory form of cell death, has been implicated in carcinogenesis and inducing necroptosis has also been considered as a therapeutic strategy. Objective We aim to evaluate the role of this pathway in gastric cancer development, prognosis and immune aspects of its tumor microenvironment. Methods and results In this study, we evaluated the gene expression of 55 necroptosis-related genes (NRGs) that were identified via carrying out a comprehensive review of the medical literature. Necroptosis pathway was deregulated in gastric cancer samples (n=375) as compared to adjacent normal tissues (n=32) obtained from the “The Cancer Genome Atlas (TCGA)”. Based on the expression of these NRGs, two molecular subtypes were obtained through consensus clustering that also showed significant prognostic difference. Differentially expressed genes between these two clusters were retrieved and subjected to prognostic evaluation via univariate cox regression analysis and LASSO cox regression analysis. A 13-gene risk signature, termed as necroptosis-related genes prognostic index (NRGPI), was constructed that comprehensively differentiated the gastric cancer patients into high- and low-risk subgroups. The prognostic significance of NRGPI was validated in the GEO cohort (GSE84437: n=408). The NRGPI-high subgroup was characterized b...