Overexpression of calpain‑1 predicts poor outcome in patients with colorectal cancer and promotes tumor cell progression associated with downregulation of FLNA.

Several studies have demonstrated that calpain-1 is involved in a variety of pathophysiological processes, including tumorigenesis. However, the clinical relevance and role of calpain-1 in colorectal cancer (CRC) are unclear. Filamin A (FLNA) is an actin-binding protein that participates in cancer progression and can be cleaved by calpain-1. In the present study, the protein expression levels of calpain-1 and FLNA were detected by immunohistochemistry in 467 matched cancerous and paracancerous tissues from patients with CRC. The staining results and the clinicopathological characteristics of the patients were comprehensively analyzed. A high expression level of calpain-1 was strongly associated with age, metastasis, Dukes stage and survival time but not with sex, histologic grade, tumour location or tumor size. By contrast, a low expression level of FLNA was significantly associated with tumor size, histological grade, metastasis, Dukes stage and survival time, but not with age, sex, or tumor location. Kaplan-Meier survival analysis demonstrated that patients with calpain-1 overexpression had a shorter mean overall survival (OS) than patients with lower levels of calpain-1 expression. Unlike high levels of calpain-1, high levels of FLNA were associated with longer OS than lower levels of FLNA expression. Furthermore, calpain-1 expression was inversely correlated with FLNA expression. The relationship between calpain-1 and FLNA was further confirmed using CRC cell lines in vitro. When calpain-1 expression decreased in CRC cells, FLNA expression increased. Furthermore, calpain-1 knockdown in CRC cells resulted in decreased proliferation, colony formation, migration and invasion. The present findings suggest that calpain-1 overexpression predicted a poor outcome in patients with CRC and promoted tumor progression, possibly via FLNA downregulation.