Wang Lan, Niu Chun-Hao, Wu Shu, Wu Hong-Mei, Ouyang Fei, He Mian, He Shan-Yang
Department of Pathogen Biology and Immunology, School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.
Department of Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.
Oncol Rep. 2016 Jan;35(1):488-96. doi: 10.3892/or.2015.4396. Epub 2015 Nov 4.
Prostate and breast cancer overexpressed 1 (PBOV1) is significantly upregulated in prostate, breast and bladder cancer, while its expression status in ovarian cancer and its clinical significance are unclear. We examined the expression levels of PBOV1 mRNA and protein in ovarian cancer cell lines and primary tissues using real-time PCR and western blotting. Immunohistochemistry was employed to analyze PBOV1 expression in 17 normal ovaries, 13 cystadenoma tissues, 14 borderline tumor tissues, and 165 clinicopathologically characterized ovarian cancers. There was negative PBOV1 expression in the 17 normal ovarian epithelial tissues. Compared to the normal ovarian epithelial cells, PBOV1 mRNA and protein were overexpressed in ovarian cancer cell lines. There was high PBOV1 protein expression in the ovarian cancer tissues from 59 of the 165 (35.8%) patients; PBOV1 expression was weak in 106 (64.2%) patients. Notably, there were significant negative associations between high PBOV1 expression and ascending histological grade, late pT/pN/pM, and International Federation of Gynecology and Obstetrics (FIGO) stage (P<0.05). Patients with high PBOV1 expression had longer overall survival; patients with low PBOV1 expression had shorter survival. Multivariate analysis revealed that PBOV1 upregulation is an independent prognostic indicator for ovarian cancer and might serve as a tumor-suppressor gene. Furthermore, PBOV1 overexpression inhibited ovarian cancer cell proliferation and tumorigenesis in vitro and in a tumor transplantation nude mouse model. In conclusion, our results suggest that PBOV1 may play an important role in suppressing ovarian cancer proliferation and carcinogenesis. PBOV1 may be a novel and useful prognostic marker and potential target for treating human ovarian cancer.
前列腺和乳腺癌过表达1(PBOV1)在前列腺癌、乳腺癌和膀胱癌中显著上调,而其在卵巢癌中的表达状况及其临床意义尚不清楚。我们使用实时PCR和蛋白质印迹法检测了卵巢癌细胞系和原发组织中PBOV1 mRNA和蛋白质的表达水平。采用免疫组织化学方法分析了17例正常卵巢、13例囊腺瘤组织、14例交界性肿瘤组织和165例具有临床病理特征的卵巢癌中PBOV1的表达情况。17例正常卵巢上皮组织中PBOV1表达呈阴性。与正常卵巢上皮细胞相比,PBOV1 mRNA和蛋白质在卵巢癌细胞系中过表达。165例患者中有59例(35.8%)的卵巢癌组织中PBOV1蛋白表达较高;106例(64.2%)患者中PBOV1表达较弱。值得注意的是,PBOV1高表达与组织学分级升高、晚期pT/pN/pM以及国际妇产科联盟(FIGO)分期之间存在显著负相关(P<0.05)。PBOV1高表达的患者总生存期较长;PBOV1低表达的患者生存期较短。多因素分析显示,PBOV1上调是卵巢癌的独立预后指标,可能作为一种肿瘤抑制基因。此外,PBOV1过表达在体外和肿瘤移植裸鼠模型中均抑制了卵巢癌细胞的增殖和肿瘤发生。总之,我们的数据表明PBOV1可能在抑制卵巢癌增殖和致癌过程中发挥重要作用。PBOV1可能是一种新型且有用的预后标志物以及治疗人类卵巢癌的潜在靶点。