Hu Hao, Xu Dan-Hua, Huang Xiao-Xu, Zhu Chun-Chao, Xu Jia, Zhang Zi-Zhen, Zhao Gang
Department of Gastrointestinal Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Department of Gastrointestinal Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, 241001, China.
J Cancer. 2018 Jan 1;9(2):346-357. doi: 10.7150/jca.19838. eCollection 2018.
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 ( < 0.01), depth of invasion (T) ( < 0.001), lymph node metastasis (N) ( < 0.001), tumor node metastasis (TNM) stage ( < 0.001) and vascular invasion ( < 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.
角蛋白17（Krt17）是角蛋白家族中一种48kDa的蛋白质成员。以往文献表明，Krt17可能在多种恶性肿瘤的进展中发挥促进作用。然而，Krt17在胃癌（GC）发生和进展中的确切功能仍不清楚。在本研究中，检测了20例新鲜GC组织及配对正常组织中Krt17的表达，发现与正常组织相比，GC组织中Krt17显著升高。然后进行免疫组化研究569例GC组织标本中Krt17的表达，发现Krt17的表达与肿瘤大小（<0.01）、浸润深度（T）（<0.001）、淋巴结转移（N）（<0.001）、肿瘤-淋巴结-转移（TNM）分期（<0.001）及血管侵犯（<0.05）显著正相关。Krt17高表达预示GC患者预后不良。此外，我们发现沉默Krt17可抑制GC细胞增殖迁移和侵袭，并通过改变Bcl2家族蛋白表达和上调裂解的caspase3诱导细胞凋亡。而且，沉默Krt17通过降低细胞周期蛋白E1和细胞周期蛋白D的表达导致细胞周期阻滞在G1/S期。总之，我们的研究结果表明Krt17可作为一种新的预测生物标志物，从而为GC患者提供新的治疗靶点。
