[基质γ-羧基谷氨酸蛋白的发现与验证：一种与胃癌TNM分期及预后相关的生物标志物]

[Discovery and verification of matrix gla protein, a TNM staging and prognosis-related biomarker for gastric cancer].

作者信息

Guo Lei, Guo Xiao-bo, Jiang Jin-ling, Zhang Jia-nian, Ji Jun, Liu Bing-ya, Zhu Zheng-gang, Yu Ying-yan

机构信息

Department of Surgery and Shanghai Institute of Digestive Surgery, Shanghai Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025, China.

出版信息

Zhonghua Bing Li Xue Za Zhi. 2010 Jul;39(7):436-41.

PMID:21055170

Abstract

OBJECTIVE

To analyze microarray datasets deposited in the public database and to identify TNM associated genes in gastric cancers.

METHODS

Microarray datasets of gastric cancer were selected from GEO database. Differentially expressed genes related to TNM staging were evaluated by significant analysis of the microarray using MultiExperiment Viewer (MEV) platform. Candidate gene expressions in gastric cancer tissues and cell lines were verified by reverse transcriptase polymerase chain reaction (RT-PCR), quantitative RT-PCR, Western blot and immunohistochemistry.

RESULTS

GES4007 dataset was re-analyzed leading to the identification of 14 genes associated with TNM staging. Over-expression of matrix gla protein (MGP) was confirmed in gastric cancer cell lines and tumor tissues by quantitative RT-PCR, Western blot and immunohistochemistry. Increased MGP expression was found in 22 of 54 cases of (40.7%) gastric cancer specimens compared to the normal gastric tissues. The up-regulation of MGP mRNA expression closely correlated with TNM stage (P = 0.001) and prognosis (P = 0.006).

CONCLUSIONS

Public databases of microarray studies are the valuable resources for data mining. MGP has been identified and confirmed as a novel biomarker for the TNM stage and prognosis of gastric cancer.

摘要

目的

分析公共数据库中存储的微阵列数据集，以鉴定胃癌中与TNM相关的基因。

方法

从基因表达综合数据库（GEO）中选择胃癌的微阵列数据集。使用多实验查看器（MEV）平台通过微阵列的显著分析来评估与TNM分期相关的差异表达基因。通过逆转录聚合酶链反应（RT-PCR）、定量RT-PCR、蛋白质免疫印迹和免疫组织化学来验证胃癌组织和细胞系中候选基因的表达。

结果

对GES4007数据集进行重新分析，从而鉴定出14个与TNM分期相关的基因。通过定量RT-PCR、蛋白质免疫印迹和免疫组织化学在胃癌细胞系和肿瘤组织中证实了基质γ-羧基谷氨酸蛋白（MGP）的过表达。与正常胃组织相比，在54例胃癌标本中的22例（40.7%）中发现MGP表达增加。MGP mRNA表达的上调与TNM分期（P = 0.001）和预后（P = 0.006）密切相关。