PDF(Pubmed)
Abstract：
Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that carries a substantial risk of morbidity and mortality. The MMP family assumes a crucial role in tumor invasion and metastasis. This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) through a comprehensive approach encompassing both computational and molecular analyses. STRING, Cytoscape, UALCAN, GEPIA, OncoDB, HPA, cBioPortal, GSEA, TIMER, ENCORI, DrugBank, targeted bisulfite sequencing (bisulfite-seq), conventional PCR, Sanger sequencing, and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC. By performing STRING and Cytohubba analyses of the 24 MMP gene family members, MMP2 (matrix metallopeptidase 2), MMP9 (matrix metallopeptidase 9), MMP12 (matrix metallopeptidase 12), and MMP16 (matrix metallopeptidase 16) genes were denoted as hub genes having highest degree scores. After analyzing MMP2, MMP9, MMP12, and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines, interestingly, all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls. The notable effect of the up-regulated MMP2, MMP9, MMP12, and MMP16 was also documented on the overall survival (OS) of the KIRC patients. Moreover, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes (MMP2, MMP9, MMP12, and MMP16). In addition to this, hub genes were involved in various diverse oncogenic pathways. The MMP gene family members (MMP2, MMP9, MMP12, and MMP16) may serve as therapeutic targets and prognostic biomarkers in KIRC.
摘要：
肾肾透明细胞癌（KIRC）是一种恶性肿瘤，具有相当大的发病率和死亡率风险。MMP家族在肿瘤侵袭和转移中起着至关重要的作用。本研究旨在通过包括计算和分子分析的综合方法，揭示MMP基因家族作为肾肾透明细胞癌（KIRC）的治疗靶标和诊断生物标志物的机制相关性。STRING,Cytoscape,UALCAN,GEPIA,OncoDB,HPA,cBioPortal,GSEA,TIMER,恩科里,DrugBank,靶向亚硫酸氢盐测序（亚硫酸氢盐-seq），常规PCR,桑格测序,本研究中使用基于RT-qPCR的分析来分析MMP基因家族成员，以准确确定可用作KIRC的治疗靶标和诊断生物标志物的一些hub基因。通过对24个MMP基因家族成员进行STRING和Cytohubba分析，MMP2（基质金属肽酶2），MMP9（基质金属肽酶9），MMP12（基质金属肽酶12），和MMP16(基质金属肽酶16)基因被表示为具有最高程度得分的hub基因。在通过各种TCGA数据库和跨临床样品和KIRC细胞系的RT-qPCR技术分析MMP2，MMP9，MMP12和MMP16之后，有趣的是,在KIRC样本中,所有这些hub基因在mRNA和蛋白水平均显著过表达,与对照组相比.也记录了上调的MMP2、MMP9、MMP12和MMP16对KIRC患者的总体存活(OS)的显著影响。此外，靶向亚硫酸氢盐测序(亚硫酸氢盐-seq)分析显示启动子低甲基化模式与hub基因(MMP2,MMP9,MMP12和MMP16)的上调相关.除此之外,hub基因参与各种不同的致癌途径。MMP基因家族成员（MMP2，MMP9，MMP12和MMP16）可能作为KIRC的治疗靶标和预后生物标志物。
