CSRP1 Drives Helicobacter pylori ‐Associated Gastric Cancer Progression via IL‐6/JAK2/STAT3‐Mediated Epithelial–Mesenchymal Transition

ABSTRACT Objective Chronic Helicobacter pylori ( H. pylori ) infection is a major risk factor for gastric cancer (GC), promoting persistent inflammation and epithelial transformation. Cysteine‐ and glycine‐rich protein 1 (CSRP1) has been implicated in tumor progression, but its role in H. pylori ‐associated gastric epithelial malignant transformation remains unclear. Methods Transcriptomic sequencing was performed on 8 paired gastric tissue samples to identify candidate genes associated with both H. pylori infection and GC. A total of 107 GC patients were included for clinical analysis. In vitro infection models were established by co‐culturing gastric epithelial cells with H. pylori (MOI 100:1) for 0–12 h, and in vivo models were generated by oral gavage of C57BL/6 mice ( n = 6 per group) with H. pylori . CSRP1 and epithelial–mesenchymal transition (EMT)‐related protein expression in gastric tissues and cells were examined using Western blotting, quantitative real‐time PCR, and immunohistochemistry. Kaplan–Meier survival analysis was conducted to evaluate prognostic relevance. Gain‐ and loss‐of‐function assays were performed to determine the effects of CSRP1 on GC cell proliferation, invasion, and downstream signaling pathways. Results CSRP1 expression was significantly elevated in GC tissues compared with adjacent normal tissues ( p < 0.01) and in GC cell lines compared with GES‐1 cells ( p < 0.01). Higher CSRP1 expression was associated with poorer overall survival in GC patients (HR = 2.26, 95% CI: 1.26–4.06, and p = 0.006). Furthermore, its expression progressively increased during the transition from H. pylori ‐associated gastritis to gastric tumorigenesis. Functional assays demonstrated that CSRP1 knockdown reduced GC cell proliferation and invasion ( p < 0.01) in vitro and suppressed tumor growth in vivo ( p < 0.01). Mechanistically, CSRP1 overexpression activated the IL‐6/JAK2/STAT3 signaling pathway, promoting partial EMT, whereas CSRP1 silencing or IL‐6 inhibition reversed these EMT‐related phenotypes ( p < 0.05). Conclusion CSRP1 promotes H. pylori –driven gastric carcinogenesis by activating EMT through the IL‐6/JAK2/STAT3 pathway. Pending further validation, targeting CSRP1 may serve as a potential prognostic biomarker and therapeutic strategy.