Zhang Tao, Wu Youliang, Fang Zheng, Yan Qiang, Zhang Shangxin, Sun Ruochuan, Khaliq Junaid, Li Yongxiang
Department of General Surgery, First Affiliated Hospital of Anhui Medical University Hefei 230000, People's Republic of China.
Am J Cancer Res. 2016 Nov 1;6(11):2679-2689. eCollection 2016.
RNA binding motif, single stranded interacting protein 3 (RBMS3) has been reported as a tumor suppressor gene (TSG) in some squamous carcinoma. However, its expression levels and clinical significance in gastric cancer (GC) remains unclear. Secreted frizzled-related protein 1 (SFRP1) plays a role of tumor suppressor in many cancers by inhibiting Wnt/β-catenin pathway. Nevertheless, its expression levels and clinical significance in GC are in dispute. In this study, quantitative real-time PCR and Western Blot were used to measure the mRNA and protein level of RBMS3 and SFRP1 in 23 fresh GC and corresponding normal tissues. Immunohistochemistry assay was performed to further measure the protein level of RBMS3 and SFRP1 on population-based tissue microarrays consisting of 172 GC cases. We found that 69.57% (16/23) and 73.91% (17/23) GC tissues expressed remarkably lower RBMS3 than the matched normal tissues respectively in mRNA and protein levels. Similarly, 78.26% (18/23) and 65.22% (15/23) GC tissues expressed lower SFRP1 than the matched normal tissues respectively in mRNA and protein levels. Additionally, the low expression of RBMS3 and SFRP1 protein were all significantly related to the poor histological grades and prognosis (all P<0.05). In multivariate analysis, RBMS3 and SFRP1 co-expression status was independent prognostic factor for GC patients. Finally, the positive correlation between expression levels (mRNA and protein) of RBMS3 and SFRP1 was observed. Overall, RBMS3 and SFRP1 are both aberrantly low expressed in GC, and RBMS3 and SFRP1 co-expression is a potential prognosis predictor of GC.
RNA结合基序单链相互作用蛋白3(RBMS3)在一些鳞状细胞癌中被报道为肿瘤抑制基因(TSG)。然而,其在胃癌(GC)中的表达水平及临床意义仍不清楚。分泌型卷曲相关蛋白1(SFRP1)通过抑制Wnt/β-连环蛋白通路在许多癌症中发挥肿瘤抑制作用。然而,其在GC中的表达水平及临床意义仍存在争议。在本研究中,采用定量实时PCR和蛋白质印迹法检测23例新鲜GC组织及相应正常组织中RBMS3和SFRP1的mRNA和蛋白质水平。进行免疫组织化学分析以进一步检测由172例GC病例组成的人群组织芯片上RBMS3和SFRP1的蛋白质水平。我们发现,分别有69.57%(16/23)和73.91%(17/23)的GC组织在mRNA和蛋白质水平上表达的RBMS3明显低于配对的正常组织。同样,分别有78.26%(18/23)和65.22%(15/23)的GC组织在mRNA和蛋白质水平上表达的SFRP1低于配对的正常组织。此外,RBMS3和SFRP1蛋白的低表达均与不良组织学分级和预后显著相关(所有P<0.05)。在多变量分析中,RBMS3和SFRP1的共表达状态是GC患者的独立预后因素。最后,观察到RBMS3和SFRP1的表达水平(mRNA和蛋白质)之间呈正相关。总体而言,RBMS3和SFRP1在GC中均异常低表达,且RBMS3和SFRP1的共表达是GC的潜在预后预测指标。