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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1553477
This article is part of the Research Topic Harnessing Big Data for Precision Medicine: Revolutionizing Diagnosis and Treatment Strategies View all 23 articles
Hypoxia-Associated Genes as Predictors of Outcomes in Gastric Cancer: A Genomic Approach
Provisionally accepted- 1 Department of Pediatric Surgery, Shengiing Hospital of China Medical University, Shenyang, China
- 2 NHC Key Laboratory of Congenital Malformation, Shengjing Hospital of China Medical University,Shenyang, Liaoning,China, Shenyang, Liaoning Province, China
To investigate the effects of hypoxia-related genes in stomach adenocarcinoma (STAD) and construct an excellent prognostic model.RNA expression data and clinical details were retrieved from the TCGA and GEO database dataset. scRNA-seq analysis was conducted on primary gastric cancer samples from GSE183904. Cellular hypoxia status was predicted using the CHPF software. WGCNA and GO-BP/KEGG enrichment of module genes analyses were performed to identify gene modules associated with hypoxia and biological pathway enrichment. A prognostic model was developed employing the LassoCox algorithm.GES-1, AGS, BGC823, and MGC803 cell lines were obtained for qRT-PCR analysis to identify the expression of model genes.Single-cell atlas within STAD delineated that most of neoplastic cells, fibroblasts, endothelial cells, and myeloid cells were hypoxic. Further analysis of neoplastic cell subpopulations identified four hypoxic subpopulations (H1-H4) and four non-hypoxic subpopulations (N1-N4), with H1 subpopulation had the highest degree of hypoxia.The prognostic model constructed by five H1-specific transcription factors EHF, EIF1AD, GLA, KEAPI, and MAGED2, was demonstrated efficacy in predicting overall survival (OS), with significantly worse OS in high-risk patients. qRT-PCR analysis determined the higher expression level of five H1-specific transcription factors in gastric cancer cell lines than that in normal gastric epithelial cell line.Hypoxia exerts a profound influence on STAD due to the overexpression of hypoxic cellular subpopulations-specific transcription factors EHF, EIF1AD, GLA, KEAPI, and MAGED2. The novel prognostic model developed by these hypoxia-associated genes presents a novel approach to risk stratification, exhibiting an excellent prognostic value for STAD patients.
Keywords: Stomach adenocarcinoma, hypoxia, single-cell RNA sequencing, Prognostic model, transcription factor, qRT-PCR
Received: 30 Dec 2024; Accepted: 21 Feb 2025.
Copyright: © 2025 Yang, Jiang and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhonghua Yang, Department of Pediatric Surgery, Shengiing Hospital of China Medical University, Shenyang, China
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