SERPINB5 promotes pancreatic adenocarcinoma progression through FBXO32-mediated regulation of epithelial-mesenchymal transition.

BACKGROUND

Pancreatic adenocarcinoma (PAAD) is a highly aggressive malignancy. This study aimed to investigate the clinical significance and biological functions of SERPINB5 in PAAD.

METHODS

Differentially expressed genes were screened from the TCGA-PAAD, GSE32676, and GSE101448 datasets. The candidate gene SERPINB5 was identified using LASSO Cox regression and receiver operating characteristic (ROC) curve analysis. SERPINB5 expression in PAAD cell lines was validated via in vitro experiments. The effects of silencing SERPINB5 on cellular phenotypes and epithelial-mesenchymal transition (EMT) were assessed using CCK-8, colony formation, and Transwell assays, as well as immunofluorescence and Western blotting. Co-immunoprecipitation (Co-IP) and rescue experiments were conducted to explore the relationship between SERPINB5 and FBXO32.

RESULTS

A risk model identified seven candidate prognostic genes, including SERPINB5. Independent single-gene ROC analysis assessed its ability to discriminate PAAD tumors from normal pancreatic tissues across three transcriptomic datasets, with areas under the curve (AUC) values of 0.851, 0.966, and 0.965. Expression analysis revealed consistently high SERPINB5 levels in both PAAD tissues and cell lines. Functional studies showed that silencing SERPINB5 inhibited PAAD cell proliferation, colony formation, migration, and invasion. Mechanistic studies indicated that SERPINB5 knockdown upregulated E-cadherin expression while downregulating Vimentin and N-cadherin levels. Co-IP experiments confirmed a physical interaction between SERPINB5 and FBXO32, and SERPINB5 knockdown resulted in reduced FBXO32 expression. Furthermore, FBXO32 overexpression reversed the malignant phenotypes and EMT-related changes caused by SERPINB5 silencing.

CONCLUSION

Our findings indicate that SERPINB5 may be a candidate diagnostic and prognostic marker for PAAD. Functionally, the SERPINB5/FBXO32 axis appears to promote PAAD progression, at least partly, through epithelial-mesenchymal transition regulation.