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Identifying and validating mmp family members(mmp2,mmp9,mmp12,and mmp16)as therapeutic targets and biomarkers in kidney renal clear cell carcinoma(KIRC)

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Oncology Research 2024年第4期32卷 737-752页

作者： KUNLUN LI DANDAN LI BARBOD HAFEZ MOUNIR M.SALEM BEKHIT YOUSEF A.BIN JARDAN FARS KAED ALANAZI EHAB I.TAHA SAYED H.AUDA FAIQAH RAMZAN MUHAMMAD JAMIL The Second Affiliated Hospital of Harbin Medical University Harbin Medical UniversityHarbinChina Department of Pharmaceutical Engineering Jiangsu Ocean UniversityLianyungangChina Department of Biological Engineering University of SalfordSalfordUK Department of Pharmaceutics College of PharmacyKing Saud UniversityRiyadhSaudi Arabia Department of Animal and Poultry Production Faculty of Veterinary and Animal SciencesGomal UniversityDera Ismail KhanPakistan Department of Arid Zone Research PARC instituteDera Ismail KhanPakistan

Kidney Renal Clear Cell Carcinoma(KIRC)is a malignant tumor that carries a substantial risk of morbidity and *** mmp family assumes a crucial role in tumor invasion and *** 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 ***,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 *** 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 *** 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 *** notable effect of the up-regulated mmp2,mmp9,mmp12,and mmp16 was also documented on the overall survival(OS)of the KIRC ***,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 *** mmp gene family members(mmp2,mmp9,mmp12,and mmp16)may serve as therapeutic targets and prognostic biomarkers in KIRC.

关键词： KIRC mmp gene family Chemotherapy Overall survival

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