Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Sci Rep. 2016 Jul 12;6:29604. doi: 10.1038/srep29604.
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.
钙蛋白酶-8 和钙蛋白酶-9 属于钙依赖性半胱氨酸蛋白酶家族，在胃中高度表达。然而，钙蛋白酶-8 和钙蛋白酶-9 在胃肿瘤发生中的作用仍知之甚少。在此，我们证明钙蛋白酶-9 在胃癌细胞系和原发性肿瘤组织中普遍降低，而钙蛋白酶-8 的表达没有明显改变。钙蛋白酶-9 而非钙蛋白酶-8 在体外诱导细胞周期停滞在 G1 期并引发细胞凋亡，并减弱体内皮下肿瘤异种移植物的生长。钙蛋白酶-9 的低表达与男性、晚期 T 期、淋巴结转移和晚期 TNM 期呈正相关。进一步分析表明，钙蛋白酶-9 是预后不良的独立预后因素，将钙蛋白酶-9 与 TNM 分期相结合可生成对患者结局更好的预测模型。总之，钙蛋白酶-9 是一种肿瘤抑制因子，可作为胃癌临床结局的潜在预后指标。
