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基质金属蛋白酶9(MMP9)、基质金属蛋白酶28(MMP28)和金属蛋白酶组织抑制剂1(TIMP1)编码基因在结直肠癌中的表达概况:对诊断和预后作用的评估

Profile of Expression of Genes Encoding Matrix Metallopeptidase 9 (MMP9), Matrix Metallopeptidase 28 (MMP28) and TIMP Metallopeptidase Inhibitor 1 (TIMP1) in Colorectal Cancer: Assessment of the Role in Diagnosis and Prognostication.

作者信息

Lorenc Zbigniew, Waniczek Dariusz, Lorenc-Podgórska Katarzyna, Krawczyk Wiktor, Domagała Maciej, Majewski Mateusz, Mazurek Urszula

机构信息

Chair and Clinical Department of General, Colorectal and Trauma Surgery, Medical University of Silesia, Sosnowiec, Poland.

Department of Propaedeutics Surgery, Chair of General, Colorectal and Polytrauma Surgery, Medical University of Silesia, Katowice, Poland.

出版信息

Med Sci Monit. 2017 Mar 15;23:1305-1311. doi: 10.12659/msm.901593.

Abstract

BACKGROUND Studies on the pathomechanism of colorectal cancer (CRC) expansion indicate a significant role of metalloproteinases and their inhibitors in the extracellular matrix. The results of the analysis of a profile of transcriptional activity of genes encoding metalloproteinases were the basis of the hypothesis indicating changes in the expression of genes encoding MMP9, MMP28, and TIMP1 as an additional diagnostic and prognostic marker of CRC. MATERIAL AND METHODS The material consisted of samples obtained from resected tumors and healthy tissue samples from 15 CRC patients (aged 46-72 years) at clinical stages (CSs) I and II-IV. Gene expression analysis was done using microarrays. Microarray data analysis was done using the GeneSpring 11.5 platform. The results were validated using the qRT-PCR technique. RESULTS We found high levels of expression of MMP9 at each CS, as well as in the tissues at the early stage of CRC. Additionally, we observed high levels of expression of TIMP1 and low levels of MMP28 genes in CS II-IV. No statistically significant differences based on the stage of CRC were observed. CONCLUSIONS MMP9 gene profile may be a complementary diagnostic marker in CRC. The results suggest a crucial role of MMP9 at the early stage of carcinogenesis in the large intestine. The increase in MMP9 and TIMP1 mRNA concentration and the decrease in MMP28 in the large intestinal tissue may be a confirmation of cancer, but it may not indicate the advance of CRC.

摘要

背景 关于结直肠癌(CRC)扩展病理机制的研究表明,金属蛋白酶及其抑制剂在细胞外基质中发挥着重要作用。对编码金属蛋白酶的基因转录活性谱进行分析的结果,是提出以下假设的基础:编码MMP9、MMP28和TIMP1的基因表达变化可作为CRC的一种额外诊断和预后标志物。

材料与方法 材料包括从15例CRC患者(年龄46 - 72岁)切除的肿瘤样本和健康组织样本,临床分期为I期以及II - IV期。使用微阵列进行基因表达分析。使用GeneSpring 11.5平台进行微阵列数据分析。结果采用qRT - PCR技术进行验证。

结果 我们发现在每个临床分期以及CRC早期组织中,MMP9均有高水平表达。此外,在II - IV期临床分期中,我们观察到TIMP1有高水平表达,而MMP28基因表达水平较低。未观察到基于CRC分期的统计学显著差异。

结论 MMP9基因谱可能是CRC中的一种辅助诊断标志物。结果表明MMP9在大肠癌变早期起着关键作用。大肠组织中MMP9和TIMP1 mRNA浓度的增加以及MMP28的减少可能是癌症的一种表现,但可能并不表明CRC的进展情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c71/5363457/a1697f28c1ce/medscimonit-23-1305-g001.jpg

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