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Integrative hdWGCNA and Machine-Learning Analysis Identifies Gastric Cancer Candidate Genes and Supports a Functional Role for KRT18.

Created on 04 Nov 2026

Authors

Yili Ran, Yufen He, Yaxi Huang, Tingting Li

Published in

Journal of visualized experiments : JoVE. Issue 237. Nov 03, 2026. Epub Nov 03, 2026.

Abstract

Gastric cancer (GC) is a frequently detected malignancy worldwide. This study aimed to identify epithelial cell-associated candidate genes in GC by integrating single-cell and bulk transcriptomic data and to explore their biological relevance using computational analyses, with in vitro functional assessment limited to KRT18. Multi-omics data were integrated to investigate the molecular mechanisms of GC. The single-cell data were processed using Seurat. Subsequently, CellChat was employed to analyze cell communication. The co-expression network of epithelial cells was constructed using high-dimensional WGCNA (hdWGCNA), and module hub genes were identified. Differential expression analysis was performed with Limma, and candidate genes were screened using LASSO and SVR-RFE. Compounds were computationally prioritized using Enrichr and DSigDB; molecular docking was not used as validation. Lastly, the biological function of KRT18 was examined in GC cells. Five candidate genes were identified: GPRC5A, KRT18, EPCAM, CLDN7, and CLDN4. These genes were associated with E2F TARGETS, GLYCOLYSIS, and OXIDATIVE PHOSPHORYLATION and correlated with multiple inferred immune-cell fractions. Drug-set enrichment nominated genistein as a computational candidate but did not establish direct binding or therapeutic efficacy. In vitro assays showed that KRT18 knockdown reduced the viability, migration, and invasion of GC cells. These findings nominate exploratory epithelial cell-associated candidate genes in GC and provide functional evidence for KRT18; further external validation is required before clinical application.

PMID:
42980250
Bibliographic data and abstract were imported from PubMed on 04 Nov 2026.

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