Zhao Hui, Wang Qingqing, Wang Xudong, Zhu Huijun, Zhang Shu, Wang Wei, Wang Zhiwei, Huang Jianfei
From the *Departments of Interventional Radiology, †General Surgery, ‡Laboratory Medicine, and §Pathology, and ∥Surgical Comprehensive Laboratory, Nantong University Affiliated Hospital, Jiangsu, China.
Pancreas. 2016 Feb;45(2):204-10. doi: 10.1097/MPA.0000000000000453.
RAB27B is a member of the Rab family GTPases involved in vesicle trafficking, and p53 has recently been implicated in regulating the exosome secretion pathway. Because exosome secretion plays an important role in modulating tumor microenvironment and invasive growth, we hypothesized that RAB27B and p53 expression might be associated with the aggressive behavior in pancreatic ductal adenocarcinoma, one of the most deadly human malignancies.
We determined protein expression of RAB27B and p53 in 260 pancreatic tissues (186 malignant and 74 normal or benign) by immunohistochemistry analysis on tissue microarray and their correlation with patients' clinical parameters and overall survival.
We found that a high RAB27B protein expression (RAB27B) was significantly associated with perineural and vascular invasion, as well as distant metastasis. Patients with a high RAB27B expression had significantly poorer overall survival in both univariate and multivariate analyses. A significant correlation between RAB27B and p53 expression was observed.
Our data indicate that RAB27B expression is an independent prognostic marker for pancreatic ductal adenocarcinoma and suggest that RAB27B-regulated exosome secretion pathway represents a novel therapeutic target in pancreatic cancer.
RAB27B是参与囊泡运输的Rab家族GTP酶成员，且p53最近被认为参与调节外泌体分泌途径。由于外泌体分泌在调节肿瘤微环境和侵袭性生长中起重要作用，我们推测RAB27B和p53的表达可能与胰腺导管腺癌（最致命的人类恶性肿瘤之一）的侵袭性行为有关。
我们通过组织微阵列的免疫组织化学分析，测定了260个胰腺组织（186个恶性组织和74个正常或良性组织）中RAB27B和p53的蛋白表达，并分析了它们与患者临床参数和总生存期的相关性。
我们发现，RAB27B蛋白高表达（RAB27B）与神经周围和血管侵犯以及远处转移显著相关。在单因素和多因素分析中，RAB27B高表达的患者总生存期均显著较差。观察到RAB27B与p53表达之间存在显著相关性。
我们的数据表明，RAB27B表达是胰腺导管腺癌的独立预后标志物，并提示RAB27B调节的外泌体分泌途径是胰腺癌的一个新的治疗靶点。
