Decreased expression of Calpain-9 predicts unfavorable prognosis in patients with gastric cancer.
Decreased expression of Calpain-9 predicts unfavorable prognosis in patients with gastric cancer.
复制标题
Calpain-9表达降低预示胃癌患者预后不良
DOI：
10.1038/srep29604
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发表时间：
2016-07-12
影响因子：
4.6
通讯作者：
Gu J
中科院分区：
文献类型：
--
作者：
Peng P;Wu W;Zhao J;Song S;Wang X;Jia D;Shao M;Zhang M;Li L;Wang L;Duan F;Zhao R;Yang C;Wu H;Zhang J;Shen Z;Ruan Y;Gu J
Calpain-8和calpain-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，calpain-8和calpain-9在胃肿瘤发生中的作用仍然知之甚少。本研究表明，calpain-9在胃癌细胞系和原发肿瘤组织中普遍降低，而calpain-8的表达没有明显改变。在体外实验中，Calpain-9（而非calpain-8）诱导细胞周期阻滞于G1期和细胞凋亡，并在体内抑制皮下肿瘤异种移植物的生长。calpain-9低表达与男性、T晚期、淋巴结转移、TNM晚期呈正相关。进一步分析发现calpain-9是不良预后的独立预后因素，将calpain-9与TNM分期相结合可以更好地预测患者预后。综上所述，calpain-9是一种肿瘤抑制因子，可作为胃癌临床预后的潜在预后指标。
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.