1. Department of Gastrointestinal Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
2. Department of Gastrointestinal Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, 241001, China
Hao Hu and Dan-hua Xu contributed equally to this article.
Krt17 is a 48kDa protein member of keratin family. Previous literatures have demonstrated Krt17 may play a promotive role in the progression of various malignancies. However, the exact function of Krt17 in the carcinogenesis and the progression of gastric cancer (GC) remains unknown. In the present study, the expression of Krt17 in 20 fresh GC and matched normal tissues were detected and Krt17 was found to be significantly increased in GC tissues compared to normal tissues. And then the immunochemistry was performed to investigate the Krt17 expression in 569 GC tissue specimens, we found that the expression of Krt17 was remarkably positively correlated with the tumor size (P < 0.01), depth of invasion (T) (P < 0.001), lymph node metastasis (N) (P < 0.001), tumor node metastasis (TNM) stage (P < 0.001) and vascular invasion (P < 0.05). High expression of Krt17 predicted a poor prognosis of GC patients. In addition, we showed silencing of Krt17 inhibited GC cell proliferation, migration and invasion, and induced cell apoptosis by altering Bcl2 family protein expression and cleaved caspase3 upregulation. Moreover, silencing of Krt17 led to cell cycle arrest at G1/S stage by decreasing cyclin E1 and cyclin D expression. In conclusion, our findings revealed Krt17 can be used as a novel predictive biomarker, thus providing a novel therapeutic target for GC patients.
Keywords: Krt17, GC, Prognosis, Proliferation, Migration and invasion, Apoptosis, Cell cycle