Wang Kun, Wang Bin, Xing Ai Yan, Xu Ke Sen, Li Guang Xin, Yu Zhen Hai
Department of General Surgery, Qianfoshan Hospital, Shandong University, 16766 Jing Shi Road, Jinan, 250014, China.
J Cancer Res Clin Oncol. 2015 May;141(5):805-12. doi: 10.1007/s00432-014-1858-1. Epub 2014 Oct 31.
Altered expression of serine protease inhibitor peptidase inhibitor clade E member 2 (SERPINE2) associates with human cancer development and progression; thus, this study investigated SERPINE2 expression in gastric cancer tissues for association with clinicopathological and survival data from the patients and then investigated the role of SERPINE2 in gastric cancer cells in vitro.
The levels of SERPINE2 mRNA in 243 gastric cancer tissues and paired non-cancerous mucosa were determined using quantitative PCR. Inhibition of SERPINE2 expression by small interfering RNA (siRNA) was detected by Western blotting. tetrazolium, soft agar, and transwell assays were performed to evaluate the proliferation, anchorage-independent growth, and motility of gastric cancer SGC7901 cells transfected with SERPINE2 siRNA.
Compared with the normal mucosa, SERPINE2 mRNA was increased in gastric cancer tissues and cells. Analysis of the 243 matched specimens showed that high SERPINE2 levels were associated with lymph node metastasis, distant metastasis, and clinical stage. Patients with high SERPINE2 mRNA levels had poorer survival compared with patients with low SERPINE2 mRNA levels. In vitro, SERPINE2 inhibited anchorage-independent growth, migration, and invasion of SGC7901 cells, but not proliferation.
Our findings indicate that upregulated SERPINE2 may contribute to the aggressive phenotype of gastric cancer and suggest that SERPINE2 can be used as a novel prognostic factor and anticancer target in patients with gastric cancer.
丝氨酸蛋白酶抑制剂E家族成员2(SERPINE2)表达改变与人类癌症的发生和发展相关;因此,本研究调查了SERPINE2在胃癌组织中的表达情况,以分析其与患者临床病理及生存数据的关联,并进一步研究SERPINE2在体外胃癌细胞中的作用。
采用定量PCR检测243例胃癌组织及配对的癌旁正常黏膜中SERPINE2 mRNA的水平。通过蛋白质印迹法检测小干扰RNA(siRNA)对SERPINE2表达的抑制作用。采用四氮唑盐法、软琼脂法和Transwell实验评估转染SERPINE2 siRNA的胃癌SGC7901细胞的增殖、非锚定依赖性生长及迁移能力。
与正常黏膜相比,胃癌组织及细胞中SERPINE2 mRNA水平升高。对243例配对标本的分析显示,SERPINE2高表达与淋巴结转移、远处转移及临床分期相关。SERPINE2 mRNA水平高的患者较SERPINE2 mRNA水平低的患者生存预后更差。在体外,SERPINE2抑制SGC7901细胞的非锚定依赖性生长、迁移和侵袭,但不影响其增殖。
我们的研究结果表明,SERPINE2上调可能导致胃癌的侵袭性表型,并提示SERPINE2可作为胃癌患者的新型预后指标和抗癌靶点。