Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
Ann Oncol. 2014 Jul;25(7):1363-1372. doi: 10.1093/annonc/mdu168. Epub 2014 May 5.
The aim of this study is to determine whether PAQR3, a protein specifically localized in the Golgi apparatus, is associated with tumor progression, metastasis and survival of human patients with gastric cancer.
PAQR3 expression status was investigated in a large panel of gastric cancer (n = 300) and their corresponding para-cancerous histological normal tissues (PCHNT) at both mRNA and protein levels. The correlation of PAQR3 expression levels with clinical features such as metastasis and prognosis was analyzed. The effect of PAQR3 on the growth and migration of gastric cancer cells was also determined.
PAQR3 was frequently down-regulated in gastric cancer samples compared with PCHNT at both mRNA and protein levels (both P < 0.0001). The expression level of PAQR3 was negatively correlated with Helicobacter pylori infection (P < 0.0001), tumor size (P < 0.0001), tumor stage (P < 0.0001), venous and lymphatic invasion (P < 0.0001), distant and nodal metastasis (P < 0.0001), and patient survival (P < 0.0001). Down-regulation of PAQR3 was highly correlated with increased epithelial-mesenchymal transition (EMT) in gastric cancer samples. In addition, PAQR3 overexpression was able to negatively modulate cell proliferation, migration and EMT of gastric cancer cells.
PAQR3 is markedly down-regulated in human gastric cancers. PAQR3 expression level is closely associated with the progression and metastasis of gastric cancers. PAQR3 is also a new genetic signature that can predict the prognosis of the patients with gastric cancer.
本研究旨在确定 PAQR3(一种特异性定位于高尔基体的蛋白质)是否与人类胃癌患者的肿瘤进展、转移和生存有关。
在大量胃癌(n=300)及其相应的癌旁组织(PCHNT)中,分别在 mRNA 和蛋白水平检测 PAQR3 的表达状态。分析 PAQR3 表达水平与转移和预后等临床特征的相关性。还测定了 PAQR3 对胃癌细胞生长和迁移的影响。
PAQR3 在胃癌样本中的表达水平在 mRNA 和蛋白水平上均明显低于 PCHNT(均 P<0.0001)。PAQR3 的表达水平与幽门螺杆菌感染(P<0.0001)、肿瘤大小(P<0.0001)、肿瘤分期(P<0.0001)、静脉和淋巴浸润(P<0.0001)、远处和淋巴结转移(P<0.0001)以及患者生存(P<0.0001)呈负相关。PAQR3 的下调与胃癌样本中上皮-间充质转化(EMT)的增加高度相关。此外,PAQR3 的过表达能够负调控胃癌细胞的增殖、迁移和 EMT。
PAQR3 在人类胃癌中明显下调。PAQR3 的表达水平与胃癌的进展和转移密切相关。PAQR3 也是一个新的遗传标志物,可预测胃癌患者的预后。