Zheng Hua-Chuan, Gong Bao-Cheng, Zhao Shuang
Department of Experimental Oncology and Animal Center, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Oncotarget. 2017 Aug 18;8(42):73017-73028. doi: 10.18632/oncotarget.20318. eCollection 2017 Sep 22.
GRP78 is a molecular chaperone located in endoplasmic reticulum, and induces folding and assembly of newly-synthesized proteins, proteasome degradation of aberrant proteins, and translocation of secretory proteins, autophagy, and epithelial-mesenchymal transition. We performed a systematic meta- and bioinformatics analysis through multiple online databases up to March 14, 2017. It was found that up-regulated GRP78 expression in gastric cancer, compared with normal mucosa at both protein and mRNA levels ( < 0.05). GRP78 expression was positively correlated with depth of invasion, TNM staging and dedifferentiation of gastric cancer ( < 0.05), while its mRNA expression was negatively correlated with depth of invasion, histological grading and dedifferentiation ( < 0.05). A positive association between GRP78 expression and unfavorable overall survival was found in patients with gastric cancer ( < 0.005). A higher mRNA expression was positively correlated with overall and progression-free survival rates of all cancer patients, even stratified by aggressive parameters, or as an independent factor ( < 0.05). These findings indicated that GRP78 expression might be employed as a potential marker to indicate gastric carcinogenesis and subsequent progression, even prognosis.
葡萄糖调节蛋白78(GRP78)是一种位于内质网的分子伴侣,可诱导新合成蛋白质的折叠与组装、异常蛋白质的蛋白酶体降解、分泌蛋白的转运、自噬以及上皮-间质转化。我们通过多个在线数据库进行了一项截至2017年3月14日的系统荟萃分析和生物信息学分析。结果发现,与正常黏膜相比,胃癌组织中GRP78在蛋白质和mRNA水平均呈上调表达(P<0.05)。GRP78表达与胃癌的浸润深度、TNM分期及去分化呈正相关(P<0.05),而其mRNA表达与浸润深度、组织学分级及去分化呈负相关(P<0.05)。在胃癌患者中发现GRP78表达与不良总生存期之间存在正相关(P<0.005)。较高的mRNA表达与所有癌症患者的总生存率和无进展生存率呈正相关,即使按侵袭性参数分层或作为独立因素时也是如此(P<0.05)。这些发现表明,GRP78表达可能作为一种潜在标志物来指示胃癌的发生、后续进展甚至预后。