ORIGINAL RESEARCH article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1541489
Prognostic and tumor microenvironmental features of gastric cancer revealed by macrophage polarization and protein lactylation-related genes
Provisionally accepted
- 1Kunming Medical University, Kunming, Yunnan Province, China
- 2Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The progression of gastric cancer (GC) is closely linked to macrophage polarization and protein lactylation; however, its underlying mechanisms remain poorly understood. This study aimed to elucidate the molecular mechanisms of GC using transcriptomic analysis.Methods: Candidate genes were identified by intersecting differentially expressed genes with key module genes associated with protein lactylation and macrophage polarization. Protein-protein interaction analysis was performed to uncover interacting genes. Prognostic genes were determined using univariate Cox regression and machine learning techniques, with model accuracy assessed via training and validation datasets.Further, enrichment analysis, immune infiltration profiling, gene mutation analysis, and drug sensitivity assessments were conducted for high-and low-risk groups.Chromosomal localization, gene-gene interaction network analysis, and expression validation of prognostic genes were also performed.Results: Two prognostic genes, ERCC6L and MYB, were identified as significant markers of prognosis through comprehensive analyses. A risk model based on these genes accurately predicted survival in patients with GC. Enrichment analysis revealed pathways such as the muscle myosin complex and adipogenesis as significantly involved in GC. Immune infiltration analysis identified 13 immune cell types, including monocytes, with strong associations to the prognostic genes. TTN, TP53, and MUC16 exhibited the highest mutation rates in both risk groups. Drug sensitivity analysis highlighted AZD.0530, CCT007093, DMOG, JNJ.26854165, and LFM.A13 as promising therapeutic candidates. ERCC6L is located on chromosome X, while MYB is located on chromosome 6. Gene-gene interaction network analysis revealed interactions between prognostic genes and other key genes. In both datasets, expression of prognostic genes was significantly higher in the GC cohort.This study identified ERCC6L and MYB as key prognostic genes, facilitating the development of a risk model that offers novel insights into potential therapeutic strategies for GC.
Keywords: gastric cancer, Prognostic genes, Macrophage polarization, Protein lactylation, Bioinformatics analysis
Received: 20 Dec 2024; Accepted: 24 Jun 2025.
Copyright: © 2025 Xu, Lei, Peng, Li, Kong, Duan, Zhang, Su and Pan. 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:
Guomiao Su, Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, China
Guoqing Pan, Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.