评估结直肠癌中 MGP 基因的表达。

Evaluation of MGP gene expression in colorectal cancer.

机构信息

ProRegeM PhD Programme in Mechanisms of Disease and Regenerative Medicine, University of Algarve, Faro 8005-139, Portugal; Centre of Marine Sciences (CCMAR), University of Algarve, Faro 8005-139, Portugal; Department of Biomedical Sciences and Medicine, University of Algarve, Faro 8005-139, Portugal.

Centre of Marine Sciences (CCMAR), University of Algarve, Faro 8005-139, Portugal; Department of Biomedical Sciences and Medicine, University of Algarve, Faro 8005-139, Portugal; Algarve Biomedical Center, University of Algarve, Faro 8005-139, Portugal.

出版信息

Gene. 2020 Jan 10;723:144120. doi: 10.1016/j.gene.2019.144120. Epub 2019 Oct 4.

DOI:10.1016/j.gene.2019.144120

PMID:31589964

Abstract

PURPOSE

Matrix Gla protein (MGP) is a vitamin K-dependent, γ-carboxylated protein that was initially found to be a physiological inhibitor of ectopic calcifications affecting mainly cartilage and the vascular system. Mutations in the MGP gene were found to be responsible for a human pathology, the Keutel syndrome, characterized by abnormal calcifications in cartilage, lungs, brain and vascular system. MGP was recently implicated in tumorigenic processes such as angiogenesis and shown to be abnormally regulated in several tumors, including cervical, ovarian, urogenital and breast. This fact has triggered our interest in analyzing the expression of MGP and of its regulator, the transcription factor runt related transcription factor 2 (RUNX2), in colorectal cancer (CRC).

METHODS

MGP and RUNX2 expression were analyzed in cancer and non-tumor biopsies samples from 33 CRC patients and 9 healthy controls by RT-qPCR. Consequently, statistical analyses were performed to evaluate the clinical-pathological significance of MGP and RUNX2 in CRC. MGP protein was also detected by immunohistochemical analysis.

RESULTS

Showed an overall overexpression of MGP in the tumor mucosa of patients at mRNA level when compared to adjacent normal mucosa and healthy control tissues. In addition, analysis of the expression of RUNX2 mRNA demonstrated an overexpression in CRC tissue samples and a positive correlation with MGP expression (Pearson correlation coefficient 0.636; p ≤ 0.01) in tumor mucosa. However correlations between MGP gene expression and clinical-pathological characteristics, such as gender, age and pathology classification did not provide relevant information that may shed light towards the differences of MGP expression observed between normal and malignant tissue.

CONCLUSIONS

We were able to associate the high levels of MGP mRNA expression with a worse prognosis and survival rate lower than five years. These results contributed to improve our understanding of the molecular mechanism underlying MGP deregulation in cancer.

摘要

目的

基质 Gla 蛋白（MGP）是一种维生素 K 依赖性的 γ-羧化蛋白，最初被发现是一种生理抑制剂，可以抑制主要影响软骨和血管系统的异位钙化。MGP 基因的突变被认为是一种人类病理学——Keutel 综合征的原因，其特征是软骨、肺、脑和血管系统的异常钙化。MGP 最近被牵连到血管生成等肿瘤发生过程中，并被证明在包括宫颈癌、卵巢癌、泌尿生殖道癌和乳腺癌在内的几种肿瘤中异常调节。这一事实引发了我们对分析结直肠癌（CRC）中 MGP 及其调节因子 runt 相关转录因子 2（RUNX2）表达的兴趣。

方法

通过 RT-qPCR 分析 33 例 CRC 患者和 9 例健康对照的癌组织和非肿瘤活检样本中的 MGP 和 RUNX2 表达。随后，进行统计分析以评估 MGP 和 RUNX2 在 CRC 中的临床病理意义。还通过免疫组织化学分析检测 MGP 蛋白。

结果

与相邻正常黏膜和健康对照组织相比，MGP 在患者肿瘤黏膜中的 mRNA 水平总体上表现出过度表达。此外，CRC 组织样本中 RUNX2 mRNA 的表达分析显示过度表达，并与 MGP 表达呈正相关（皮尔逊相关系数 0.636；p≤0.01）在肿瘤黏膜中。然而，MGP 基因表达与临床病理特征（如性别、年龄和病理分类）之间的相关性并没有提供可能阐明正常组织和恶性组织之间观察到的 MGP 表达差异的相关信息。