He Yun, Ye Mengsi, Zhou Lingling, Shan Yunfeng, Lu Guangrong, Zhou Yuhui, Zhong Jinwei, Zheng Jihang, Xue Zhanxiong, Cai Zhenzhai
Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Department of Pathology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Int J Oncol. 2017 Feb;50(2):396-404. doi: 10.3892/ijo.2016.3828. Epub 2016 Dec 30.
Some studies have demonstrated that Rab11-family interacting proteins (Rab11-FIPs) are connected with the tumorigenesis, and they may act as tumor promoters in some cancers. The clinicopathological significance of Rab11-family interacting protein 4 (Rab11-FIP4 ) expression and its possible effects on pancreatic cancer (PC) are still undiscovered. In this study, Rab11-FIP4 protein expression level in 60 PC specimens and pair-matched non-cancerous samples were detected by immunohistochemistry analysis. The results were analysed and compared with each patients' clinical data. Rab11-FIP4 expression in PC tissues increased significantly more than that of adjacent non-cancerous tissues (P=0.0001). Overexpression of Rab11-FIP4 in the PC tissues was significantly related to tumor size (P=0.0001), histological grade (P=0.028), metastasis (P=0.001) and TNM stage (P=0.004) but not with age (P=0.832), gender (P=0.228) or tumor site (P=0.875). Kaplan-Meier survival analysis showed that overexpression of Rab11-FIP4 was significantly related to overall survival time (P=0.0036). In addition, Rab11-FIP4 in PANC-1 pancreatic cancer cells were successfully knocked-out using the CRISPR/Cas9 system. Rab11-FIP4 knockout in PANC-1 cells inhibited cell growth, invasion and metastasis, and arrested cell cycle progression, but did not alter apoptosis. Our findings suggest that overexpression of Rab11-FIP4 predicts poor clinical outcomes for pancreatic cancer and contributes to pancreatic tumor progression.
一些研究表明,Rab11家族相互作用蛋白(Rab11-FIPs)与肿瘤发生有关,并且它们在某些癌症中可能充当肿瘤促进因子。Rab11家族相互作用蛋白4(Rab11-FIP4)表达的临床病理意义及其对胰腺癌(PC)的可能影响仍未被发现。在本研究中,通过免疫组织化学分析检测了60例PC标本和配对的非癌样本中Rab11-FIP4蛋白的表达水平。对结果进行分析并与每位患者的临床数据进行比较。PC组织中Rab11-FIP4的表达明显高于相邻的非癌组织(P = 0.0001)。PC组织中Rab11-FIP4的过表达与肿瘤大小(P = 0.0001)、组织学分级(P = 0.028)、转移(P = 0.001)和TNM分期(P = 0.004)显著相关,但与年龄(P = 0.832)、性别(P = 0.228)或肿瘤部位(P = 0.875)无关。Kaplan-Meier生存分析表明,Rab11-FIP4的过表达与总生存时间显著相关(P = 0.0036)。此外,使用CRISPR/Cas9系统成功敲除了PANC-1胰腺癌细胞中的Rab11-FIP4。PANC-1细胞中Rab11-FIP4的敲除抑制了细胞生长、侵袭和转移,并阻止了细胞周期进程,但未改变细胞凋亡。我们的研究结果表明,Rab11-FIP4的过表达预示着胰腺癌的临床预后不良,并促进胰腺肿瘤进展。