Abstract
Calpain-8 and calpain-9 belong to the family of calcium-dependent cysteine proteases, which are highly expressed in the stomach. However, the roles of calpain-8 and calpain-9 in gastric tumorigenesis remain little understood. Herein, we demonstrated that calpain-9 was generally decreased in gastric cancer cell lines and primary tumor tissues, while calpain-8 expression was not significantly altered. Calpain-9, but not calpain-8, induced cell cycle arrest in the G1 phase and cellular apoptosis in vitro, and it attenuated the growth of subcutaneous tumor xenografts in vivo. Low expression of calpain-9 was positively associated with male sex, late T stage, lymph node metastasis, and advanced TNM stage. Further analysis identified calpain-9 as an independent prognostic factor for poor prognosis, and combining calpain-9 with TNM stage generated a better predictive model for patient outcomes. In conclusion, calpain-9 is a tumor suppressor that can be regarded as a potential prognosis indicator for clinical outcomes in gastric cancer.
Highlights
The relative mRNA expression of calpain-8 was reduced in gastric cancer from the GSE13911 dataset, whereas its mRNA levels were increased in gastric cancer from the TCGA-STAD dataset (Fig. 1a and Supplementary Fig. S1b)
The changes of calpain-8 mRNA levels in different gastric cancer cell lines were discordant (Fig. 1e). These results suggested that calpain-9 expression is decreased in gastric cancer
In addition to traditional tumor-node-metastasis (TNM) stage, gastric cancer is divided into intestinal, mixture and diffuse types by the Lauren classification system[17,18]
Summary
Results indicated that by comparing with GES-1 cell line, the expression of calpain-9 at the mRNA and protein levels was significantly decreased in all gastric cancer cell lines (Fig. 1d,e). The protein levels of calpain-8 in gastric cancer cell lines were comparable with that in GES-1 cells (Fig. 1d). The changes of calpain-8 mRNA levels in different gastric cancer cell lines were discordant (Fig. 1e).
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