Comprehensive analysis of genomic alterations, clinical outcomes, putative functions and potential therapeutic value of MMP11 in human breast cancer

Autor: Gopisetty Gopal, Aparna Natarajan, Prarthana Gopinath, Oviya Revathi Paramasivam, Amritha Sathyanarayanan
Rok vydání: 2020
Předmět:
Zdroj: Gene Reports. 21:100852
ISSN: 2452-0144
DOI: 10.1016/j.genrep.2020.100852
Popis: The aim of the current study is to comprehend the prognostic and therapeutic value of matrix metalloproteinase (MMP11) in breast cancer using computational analyses. Gene expression-based Outcome for Breast cancer Online (GOBO) analysis revealed that MMP11 expression was increased in tumor when compared to normal. Among the subtypes, human epidermal growth factor receptor 2 (HER2) enriched and estrogen receptor (ER) positive showed higher expression of MMP11. The results were independently validated with cBioPortal and Oncomine databases. Tumors with high MMP11 expression showed poor overall survival and distant metastasis free survival. Further, protein-protein interactome network was constructed and molecular pathway analysis using Reactome database identified its putative role in diverse cellular processes. In addition, UALCAN web portal revealed hypomethylation in the promoter region of MMP11 in breast tumors. Molecular docking using iGEMDOCK and Autodock Vina were performed to identify natural compounds and repurposed drugs interaction with MMP11. Our study confirms the prognostic significance of MMP11 in breast cancer and their intrinsic subtypes. Twelve bio-compounds which were predominantly flavonoids and anti-psychotic drug pimozide showed significant docking scores with MMP11. Further, potential of these compounds in inhibiting MMP11 related molecular pathways and in targeting breast cancer cells are yet to be studied.
Databáze: OpenAIRE
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