Kairui Wu,1,* Yu Ye,1,* Bei Pei,1 Biao Song,2 Tingting Li,2 Qi Yang,2 Yueping Jin,2 Xuejun Li2 

1Graduate School, Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 2Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yueping Jin, Email 419513543@qq.com Xuejun Li, Email lixuejun0308@126.com

Background: Gastric cancer (GC) is a major global health burden, and chronic atrophic gastritis (CAG), a key precancerous lesion in the Correa cascade, is critical in its pathogenesis. As a Ca²+-dependent actin-regulating protein, scinderin (SCIN) has been implicated in tumor progression across multiple malignancies, including gastric cancer. This study investigated SCIN expression dynamics during CAG-to-GC progression, its association with the tumor immune microenvironment (TIME) and clinical prognosis, and validated its role via integrated bioinformatics and experiments.
Methods: Transcriptomic data from TCGA and GEO were analyzed using R. WGCNA and ceRNA networks identified SCIN as the core RNA and its interacting miRNAs/lncRNAs. GSVA, GSEA, immune infiltration, and checkpoint analyses explored SCIN’s immunological relevance. Prognostic value was assessed via Cox models and ROC curves. SCIN expression was validated in 28 human gastric tissues by RT-qPCR and Western blotting. Functional assays (CCK-8, Transwell, flow cytometry) investigated its role in GC cells.
Results: SCIN expression significantly increased along normal mucosa→CAG→GC, with high diagnostic performance (AUC). Elevated SCIN correlated with poor survival and served as an independent prognostic factor. It was involved in immune-related pathways, modulated the TIME, and correlated with immune checkpoint markers. SCIN knockdown inhibited GC cell migration, enhanced apoptosis, and altered cell cycle.
Conclusion: This study is the first to identify SCIN as a key molecular driver in the CAG-to-GC transition. SCIN represents a robust prognostic biomarker and a potential target for immunotherapeutic intervention in GC.

Keywords: SCIN, gastric cancer, chronic atrophic gastritis, Correa cascade, immunity