94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1562395
This article is part of the Research Topic Integrating Molecular Mechanisms, Immunotherapy, and Drug Sensitivity in Cancer Immunology and Oncology View all 19 articles
Integrative Analysis of Single-Cell and Bulk RNA Sequencing Reveals the Oncogenic Role of ANXA5 in Gastric Cancer and Its Association with Drug Resistance
Provisionally accepted- 1 Department of General Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China, Shiyan, China
- 2 Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central Minzu University, Wuhan, China, Wuhan, Hebei Province, China
- 3 Department of Endocrinology, Taihe Hospital, Hubei University of Medicine, Shiyan, China, Shiyang, China
- 4 Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, China, Shiyan, China
Background: Gastric cancer (GC) remains a leading cause of cancer-related mortality, with over one million new cases and 769,000 deaths reported in 2020. Despite advancements in chemotherapy, surgery, and targeted therapies, delayed diagnosis due to overlooked early symptoms leads to poor prognosis.We integrated bulk RNA sequencing and single-cell RNA sequencing datasets from TCGA, GEO, and OMIX001073, employing normalization, batch effect correction, and dimensionality reduction methods to identify key cell populations associated with GC invasion and epithelial-mesenchymal transition (EMT), as well as analyze the tumor immune microenvironment.Results: Our analysis identified the MUC5AC+ malignant epithelial cell cluster as a significant player in GC invasion and EMT. Cluster 1, representing this cell population, exhibited higher invasion and EMT scores compared to other clusters. Survival analysis showed that high abundance in cluster 0 correlated with improved survival rates (P=0.012), whereas cluster 1 was associated with poorer outcomes (P=0.045). A prognostic model highlighted ANXA5 and GABARAPL2 as two critical genes upregulated in GC tumors. High-risk patients demonstrated increased immune cell infiltration and worse prognosic. Analysis of tumor mutation burden (TMB) indicated that patients with low TMB in the high-risk group had the worst prognosis. Wet-lab validation experiments confirmed the oncogenic role of ANXA5, showing its facilitation of cell proliferation, invasion, and migration while suppressing apoptosis.This study offers novel insights into the subpopulations of malignant epithelial cells in GC and their roles in tumor progression. It provides a prognostic model and potential therapeutic targets to combat GC, contributing crucial understanding to the fundamental mechanisms of drug resistance in gastrointestinal cancers.
Keywords: gastric cancer, single-cell RNA sequencing, Prognostic model, Immune infiltration, drug sensitivity
Received: 17 Jan 2025; Accepted: 18 Feb 2025.
Copyright: © 2025 Chen, Zhang, Gong, Wei, Bai, Zhang and Yu. 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:
Chen Bai, Department of General Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China, Shiyan, China
Tingting Zhang, Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, China, Shiyan, China
Guanghui Yu, Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central Minzu University, Wuhan, China, Wuhan, Hebei Province, 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.