Cheng Xiao-Bo, Sato Norihiro, Kohi Shiro, Koga Atsuhiro, Hirata Keiji
1. Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan ; 2. Department of Breast Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
1. Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
J Cancer. 2015 Sep 3;6(11):1093-8. doi: 10.7150/jca.12990. eCollection 2015.
Receptor for hyaluronic acid (HA)-mediated motility (RHAMM) is a nonintegral cell surface receptor involved in the aggressive phenotype in a wide spectrum of human malignancies, but the significance of RHAMM in pancreatic ductal adenocarcinoma (PDAC) remains unknown. In this study, we investigated the expression of RHAMM and its clinical relevance in PDAC. RHAMM mRNA expression was examined in 8 PDAC cell lines and in primary pancreatic cancer and adjacent non-tumor tissues from 14 patients using real-time RT-PCR. Western blotting was carried out to analyze the expression of RHAMM protein in PDAC cell lines. We also investigated the expression patterns of RHAMM protein in tissue samples from 70 PDAC patients using immunohistochemistry. The RHAMM mRNA expression was increased in some PDAC cell lines as compared to a non-tumorous pancreatic epithelial cell line HPDE. The RHAMM mRNA expression was significantly higher in PDAC tissues as compared to corresponding non-tumorous pancreatic tissues (P < 0.0001). The RHAMM protein expression was higher in the vast majority of PDAC cell lines relative to the expression in HPDE. The immunohistochemical analysis revealed strong expression of RHAMM in 52 (74%) PDAC tissues. Strong expression of RHAMM was significantly associated with a shorter survival time (P = 0.038). In multivariate analysis, tumor stage (P = 0.039), residual tumor (P = 0.015), and strong RHAMM expression (P = 0.034) were independent factors predicting poor survival. Strong expression of RHAMM may predict poor survival in PDAC patients and may provide prognostic and, possibly, therapeutic value.
透明质酸(HA)介导的运动受体(RHAMM)是一种非整合性细胞表面受体,参与多种人类恶性肿瘤的侵袭性表型,但RHAMM在胰腺导管腺癌(PDAC)中的意义仍不清楚。在本研究中,我们调查了RHAMM在PDAC中的表达及其临床相关性。使用实时RT-PCR检测了8种PDAC细胞系以及14例患者的原发性胰腺癌组织和相邻非肿瘤组织中RHAMM mRNA的表达。进行蛋白质印迹分析以检测PDAC细胞系中RHAMM蛋白的表达。我们还使用免疫组织化学研究了70例PDAC患者组织样本中RHAMM蛋白的表达模式。与非肿瘤性胰腺上皮细胞系HPDE相比,一些PDAC细胞系中RHAMM mRNA表达增加。与相应的非肿瘤性胰腺组织相比,PDAC组织中RHAMM mRNA表达显著更高(P < 0.0001)。相对于HPDE中的表达,绝大多数PDAC细胞系中RHAMM蛋白表达更高。免疫组织化学分析显示,52例(74%)PDAC组织中RHAMM呈强表达。RHAMM强表达与较短的生存时间显著相关(P = 0.038)。在多变量分析中,肿瘤分期(P = 0.039)、残留肿瘤(P = 0.015)和RHAMM强表达(P = 0.034)是预测生存不良的独立因素。RHAMM强表达可能预测PDAC患者生存不良,并可能提供预后价值,甚至可能具有治疗价值。