Receptor for Hyaluronic Acid-Mediated Motility is Associated with Poor Survival in Pancreatic Ductal Adenocarcinoma.
Receptor for Hyaluronic Acid-Mediated Motility is Associated with Poor Survival in Pancreatic Ductal Adenocarcinoma.
复制标题
透明质酸介导的运动的受体与胰腺导管腺癌中的存活不良有关。
DOI：
10.7150/jca.12990
复制
发表时间：
2015
影响因子：
3.9
通讯作者：
Hirata K
中科院分区：
文献类型：
--
作者：
Cheng XB;Sato N;Kohi S;Koga A;Hirata K
透明质酸介导的运动受体（RHAMM）是一种非整合的细胞表面受体，与多种恶性肿瘤的侵袭表型有关，但其在胰腺导管腺癌（PDAC）中的意义尚不清楚。在这项研究中，我们研究了RHAMM在PDAC中的表达及其临床意义。采用实时荧光定量RT-PCR检测8种PDAC细胞系和14例原发性胰腺癌及癌旁非肿瘤组织中RHAMM mRNA的表达。Western blotting检测PDAC细胞中RHAMM蛋白的表达。我们还研究了RHAMM蛋白的表达模式，从70 PDAC患者的组织样本，使用免疫组织化学。与非肿瘤性胰腺上皮细胞系HPDE相比，在一些PDAC细胞系中RHAMM mRNA表达增加。PDAC组织中RHAMM mRNA的表达显著高于相应的非肿瘤胰腺组织（P < 0.0001）。相对于HPDE中的表达，在绝大多数PDAC细胞系中RHAMM蛋白表达更高。免疫组化结果显示，52例（74%）PDAC组织中RHAMM呈强阳性表达。RHAMM的强表达与较短的生存时间显著相关（P = 0.038）。在多因素分析中，肿瘤分期（P = 0.039），残留肿瘤（P = 0.015）和强RHAMM表达（P = 0.034）是预测生存不良的独立因素。RHAMM的强表达可能预测PDAC患者的生存率，并可能提供预后和治疗价值。
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.