Li Bing-Qi, Huang Shuai, Shao Qian-Qian, Sun Jian, Zhou Li, You Lei, Zhang Tai-Ping, Liao Quan, Guo Jun-Chao, Zhao Yu-Pei
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, P.R. China.
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, P.R. China.
Oncol Lett. 2017 Apr;13(4):2531-2538. doi: 10.3892/ol.2017.5784. Epub 2017 Feb 28.
Although Wilms tumor 1 (WT1)-associated protein (WTAP) was initially found to be a specific WT1-binding protein, it has increasingly attracted attention because of its oncogenic role in various types of malignancies, including cholangiocarcinoma, glioblastoma and acute myeloid leukemia. However, the clinical impact of WTAP on pancreatic ductal adenocarcinoma (PDAC) is still unknown. A total of 145 patients who underwent surgical treatment from 2004 to 2008 were enrolled in the present study. The cytoplasmic and nuclear expression of WTAP in tumor and adjacent normal tissues was examined by immunohistochemical analysis in order to investigate the relationship between WTAP and the clinicopathological factors and prognosis of patients with PDAC. The nuclear and cytoplasmic expression of WTAP in tumor tissues was significantly higher compared with non-tumor tissues (P<0.001). High expression of WTAP in the nucleus was significantly associated with gender (P=0.010) and tumor stage (P=0.020), while high expression of WTAP in the cytoplasm was significantly associated with gender (P=0.018), histological grade (P=0.047) and perineural invasion (P=0.028). In addition, a univariate analysis revealed that high nuclear expression of WTAP in tumor tissues was significantly associated with poor overall survival (P<0.001), as well as several clinicopathological variables, including gender and N stage. In a multivariate Cox regression analysis, nuclear WTAP expression was identified as an independent prognostic indicator for PDAC (relative risk, 1.855; 95% confidence interval, 1.033-3.333; P=0.039). The results of the present study indicated that high nuclear expression of WTAP is a valuable molecular biomarker of a poor prognosis among patients with PDAC.
尽管威尔姆斯瘤1（WT1）相关蛋白（WTAP）最初被发现是一种特异性WT1结合蛋白，但由于其在包括胆管癌、胶质母细胞瘤和急性髓系白血病在内的各种恶性肿瘤中的致癌作用，它越来越受到关注。然而，WTAP对胰腺导管腺癌（PDAC）的临床影响仍不清楚。本研究纳入了2004年至2008年接受手术治疗的145例患者。通过免疫组织化学分析检测WTAP在肿瘤及相邻正常组织中的细胞质和细胞核表达，以研究WTAP与PDAC患者临床病理因素及预后之间的关系。与非肿瘤组织相比，肿瘤组织中WTAP的细胞核和细胞质表达显著更高（P<0.001）。WTAP在细胞核中的高表达与性别（P=0.010）和肿瘤分期（P=0.020）显著相关，而WTAP在细胞质中的高表达与性别（P=0.018）、组织学分级（P=0.047）和神经周围侵犯（P=0.028）显著相关。此外，单因素分析显示，肿瘤组织中WTAP的高细胞核表达与总体生存率差（P<0.001）以及包括性别和N分期在内的几个临床病理变量显著相关。在多因素Cox回归分析中，细胞核WTAP表达被确定为PDAC的独立预后指标（相对风险，1.855；95%置信区间，1.033 - 3.333；P=0.039）。本研究结果表明，WTAP的高细胞核表达是PDAC患者预后不良的有价值分子生物标志物。
