Multi-bioinformatics revealed potential biomarkers and repurposed drugs for gastric adenocarcinoma-related gastric intestinal metaplasia

Sep 21, 2026

Uploaded by Skyler

Biomarkers linked to progression from gastric intestinal metaplasia (GIM) to gastric adenocarcinoma (GA), specifically GA-related GIM, can improve identification of patients at elevated risk. This study applied multi-bioinformatics integrating microarray gene expression, single-cell RNA-seq cell-type identification, pathway and network analyses, enrichment resources, and molecular docking with immunohistochemistry. Paired surgical biopsies from 16 GIM-GA patients provided 64 samples for gene expression matrices, and co-analysis incorporated endoscopic biopsy scRNA-seq and immunohistochemistry data from 37 patients.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Biomarker rationale for GA-related GIM

Clinical background and current surveillance guidance

Multi-bioinformatics workflow and datasets

Candidate biomarkers and signaling networks

Repurposed drug targets and validation approach

npj | systems biology and applications Article | Published in partnership with the Systems Biology Institute | | | | --- | --- | --- | | [https://doi.org/10.1038/s41540-024-00455-0](https://doi.org/10.1038/s41540-024-00455-0) | | | | Multi-bioinformatics revealed potential biomarkers and repurposed drugs for gastric adenocarcinoma-related gastric intestinal metaplasia
Check for updates | | | | Gøran Troseth Andersen1,2,3, Aleksandr Ianevski1, Mathilde Resell1, Naris Pojskic4, Hanne-Line Rabben1, Synne Geithus1, Yosuke Kodama1, Tomita Hiroyuki5, Denis Kainov 1, Jon Erik Grønbech1,2,
Yoku Hayakawa6, Timothy C. Wang7, Chun-Mei Zhao 1 & Duan Chen 1 | | | | Biomarkers associated with the progression from gastric intestinal metaplasia (GIM) to gastric adenocarcinoma (GA), i.e., GA-related GIM, could provide valuable insights into identifying patients with increased risk for GA. The aim of this study was to utilize multi-bioinformatics to reveal potential biomarkers for the GA-related GIM and predict potential drug repurposing for GA prevention inpatients. The multi-bioinformatics included gene expression matrix (GEM) by microarray gene expression (MGE), ScType (a fully automated and ultra-fast cell-type identiﬁcation based solely on a given scRNA-seq data), Ingenuity Pathway Analysis, PageRank centrality, GO and MSigDB enrichments, Cytoscape, Human Protein Atlas and molecular docking analysis in combination with immunohistochemistry. To identify GA-related GIM, paired surgical biopsies were collected from 16 GIM-GA patients who underwent gastrectomy, yielding 64 samples (4 biopsies per stomach x 16 patients) for MGE. Co-analysis was performed by including scRNAseq and immunohistochemistry datasets of endoscopic biopsies of 37 patients. The results of the present study showed potential biomarkers for GA-related GIM, including GEM of individual patients, individual genes (such as RBP2 and CD44), signaling pathways, network of molecules, and network of signaling pathways with key topological nodes. Accordingly, potential treatment targets with repurposed drugs were identiﬁed including epidermal growth factor receptor, proto-oncogene tyrosine-protein kinase Src, paxillin, transcription factor Jun, breast cancer type 1 susceptibility protein, cellular tumor antigen p53, mouse double minute 2, and CD44 . | | | | The prevalence of gastric intestinal metaplasia (GIM) is approximately 15% in those undergoing routine endoscopy in Europe1,2. GIM can be found in approximately 50% of patients with gastric ulcers and almost 100% of patients with intestinal type gastric adenocarcinoma (GA), the major subtype of gastric cancer3. According to Correa’s cascade4, the progression rate from GIM toGA varies from0.25%to42%during a course of5years5,6, and this malignant conversion can occur even after H. pylori eradication7,8. | Nevertheless, it remains unclear whether GIM glands can directlytransform into GA or share aclonal origin9–11, despite GIM being susceptible to somatic mutations and copy number aberrations commonly found in GA12.
Currently, the American Gastroenterological Association (AGA), the European Society of Gastrointestinal Endoscopy and the British Society of Gastroenterology recommend no further intervention against GIM, except for the eradication of H. pylori13–15. Of note, in patients with GIM, the AGA | | 1Department of Clinical and Molecular Medicine, Norwegian University of Science andTechnology(NTNU), Trondheim, Norway. 2Department of Surgery, St. Olav’s Hospital, Trondheim, Norway. 3Department of Surgery, Namsos Hospital, Namsos, Norway. 4Laboratory for Bioinformatics and Biostatistics, University of Sarajevo-Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and Herzegovina. 5Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan. 6Department of Gastroenterology, Tokyo University Hospital, Tokyo, Japan. 7Department of Digestive and Liver Diseases and Her

FAQs

What problem does the study target regarding gastric intestinal metaplasia?

It focuses on finding biomarkers that clarify risk of progression from gastric intestinal metaplasia (GIM) to gastric adenocarcinoma (GA), especially GA-related GIM.

Which analytical approaches were combined to discover biomarkers and drug candidates?

The workflow integrates gene expression matrix analysis from microarrays, scRNA-seq cell-type identification (ScType), pathway and centrality measures, enrichment analyses, network construction (including Cytoscape), human protein localization (Human Protein Atlas), molecular docking, and immunohistochemistry.

How were the samples collected and used in the analyses?

Paired surgical biopsies were collected from 16 GIM-GA patients who underwent gastrectomy, yielding 64 samples for microarray gene expression analysis. Co-analysis additionally included scRNA-seq and immunohistochemistry datasets from endoscopic biopsies of 37 patients.

Sep 21, 2026

Uploaded by Skyler