Zheng Hua-chuan, Takahashi Hiroyuki, Li Xiao-han, Hara Takuo, Masuda Shinji, Guan Yi-fu, Takano Yasuo
Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang 110003, China.
Hum Pathol. 2008 Jul;39(7):1042-9. doi: 10.1016/j.humpath.2007.11.009. Epub 2008 May 14.
Glucose-related proteins (GRPs) are ubiquitously expressed in endoplasmic reticulum and able to assist in protein folding and assembly; consequently, they are considered as molecular chaperones. GRP78 and GRP94 expression was induced by glucose starvation and up-regulated in the malignancies. To clarify the roles of both molecules in tumorigenesis and progression of gastric carcinomas, immunohistochemistry was used on tissue microarray containing gastric carcinomas, adenomas, and nonneoplastic mucosa using the antibodies against GRP78 and GRP94, with a comparison of their expression with clinicopathological parameters of carcinomas. Gastric carcinoma cell lines (MKN28, AGS, MKN45, KATO-III, and HGC-27) were studied for both proteins by immunohistochemistry and Western blot. There was more expression of both proteins in gastric carcinoma and adenoma than in nonneoplastic mucosas (P < .05). All gastric carcinoma cell lines showed their expression at different levels. They were positively correlated with tumor size, depth of invasion, lymphatic and venous invasion, lymph node metastasis, and Union Internationale Contre le Cancer staging (P < .05), with positive relationship between both proteins (P < .05). Univariate analysis indicated the postsurgical cumulative survival rate of patients with positive GRP78 or GRP94 expression to be lower than that in those without GRP78 or GRP94 expression (P < .05), but the close link disappeared if stratified according to depth of invasion (P > .05). Multivariate analysis showed that age, depth of invasion, lymphatic invasion, lymph node metastasis, Union Internationale Contre le Cancer staging, and Lauren classification (P < .05), but not GRP78 and GRP94 expression, were independent prognostic factors for carcinomas (P > .05). Up-regulated expression of GRP78 and GRP94 was possibly involved in pathogenesis, growth, invasion, and metastasis of gastric carcinomas. They were considered objective and effective markers for the aggressive behavior and poor prognosis in gastric carcinomas.
葡萄糖相关蛋白(GRPs)在内质网中广泛表达,能够协助蛋白质折叠和组装;因此,它们被视为分子伴侣。葡萄糖饥饿可诱导GRP78和GRP94表达,并在恶性肿瘤中上调。为阐明这两种分子在胃癌发生发展中的作用,我们使用抗GRP78和GRP94抗体,对包含胃癌、腺瘤和非肿瘤性黏膜的组织芯片进行免疫组织化学分析,并将它们的表达与癌的临床病理参数进行比较。通过免疫组织化学和蛋白质印迹法研究了胃癌细胞系(MKN28、AGS、MKN45、KATO-III和HGC-27)中的这两种蛋白。胃癌和腺瘤中这两种蛋白的表达均高于非肿瘤性黏膜(P < 0.05)。所有胃癌细胞系均显示出不同水平的表达。它们与肿瘤大小、浸润深度、淋巴管和静脉浸润、淋巴结转移以及国际抗癌联盟分期呈正相关(P < 0.05),且两种蛋白之间呈正相关(P < 0.05)。单因素分析表明,GRP78或GRP94表达阳性患者的术后累积生存率低于GRP78或GRP94表达阴性患者(P < 0.05),但根据浸润深度分层后,这种密切联系消失(P > 0.05)。多因素分析显示,年龄、浸润深度、淋巴管浸润、淋巴结转移、国际抗癌联盟分期和劳伦分类(P < 0.05)是癌的独立预后因素,而GRP78和GRP94表达不是(P > 0.05)。GRP78和GRP94表达上调可能参与了胃癌的发病机制、生长、浸润和转移。它们被认为是胃癌侵袭性和预后不良的客观有效标志物。