Calpain 8 as a potential biomarker regulates the progression of pancreatic cancer via EMT and AKT/ERK pathway

Calpain is a non-lysozyme, calcium-dependent intracellular cysteine protease that has been shown to play a role in tumor proliferation, survival, migration, invasion, and apoptosis. Dysregulation of calpain expression is closely related to tumorigenesis. However, the role of calpain-8 (CAPN8), as a member of the calpain family, in pancreatic cancer (PC) is remains unclear. In elucidating the mechanism of CAPN8 in PC, a comprehensive bioinformatics analysis and in vitro experiments were conducted. The TCGA database was used to explore the expression level of CAPN8, and the results in PC tissues and cell lines were verified. Then, the correlation between CAPN8 and clinicopathological features was analyzed. Additionaly, promoter methylation, immune infiltration, and GO/KEGG enrichment analyses were performed. Lastly, the molecular mechanism of CAPN8 in PC was investigated by using cell counting kit (CCK) 8, transwell, wound healing, Western blot assays, and so on. Results indicate that CAPN8 was highly expressed in PC and correlated with poor prognosis and advanced TNM stage. In addition, a low level of immune infiltration was closely associated with the high expression level of CAPN8. Based on these findings, we hypothesized that CAPN8 is a potential biomarker that regulates progression of PC via EMT and the AKT/ERK pathway. SIGNIFICANCE: Through comprehensive biological information and in vitro experiments, CAPN8 has been confirmed to play an important role in regulating pancreatic cancer (PC) proliferation, migration and invasion. CAPN8 is found to be closely related to the diagnosis, survival and prognosis of PC. Above all, CAPN8 may be a potential biomarker for the diagnosis and prognosis of PC.