Prognostic Significance and Metastatic Potential of MMPs and TIMPs in Breast Cancer; An In-Silico Study

Rashid Mehmood

Abstract


Background: Matrix metalloproteinase (MMP) family and its endogenous tissue inhibitors (TIMPs) play central roles in regulating extracellular matrix (ECM) dynamics, thereby contributing to breast cancer progression and metastatic spread. A thorough genomic analysis of the genes coding for the members of MMPs and TIMPs in breast cancer for their prognosis and metastatic potential is lacking.

Methods: In this study, data from The Cancer Genome Atlas (TCGA) Pan-Cancer Atlas, the Genotype-Tissue Expression (GTEx) and publicly available breast cancer microarray datasets were integrated for comprehensive analysis of genetic alterations, transcriptomic dysregulation, prognostic significance and metastatic potential of MMP and TIMP genes in breast cancer.

Results: The findings revealed marked genetic alterations across MMP and TIMP genes, with gene amplification being the most prevalent mutation type. In addition to genetic alterations, substantial upregulation of MMP1, MMP9, MMP11, and TIMP1, while downregulation of MMP19, MMP27, and TIMP4 were observed. Prognostic evaluation using Kaplan-Meier analysis revealed that overexpression of TIMP1 and TIMP4 correlates with better overall survival, whereas high expression of MMP1, MMP8, and MMP13 are linked to poor outcomes.

Conclusions: These findings demonstrate potential clinical value of MMPs and TIMPs as biomarkers for breast cancer prognosis and diagnosis. Additionally, the study highlights the therapeutic promise of targeting the MMP-TIMP axis to modulate ECM dynamics and impede tumor progression and metastasis.

Keywords

Breast Cancer, Systems genomics, MMPs, TIMPs, Genomics, Prognosis


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DOI: https://doi.org/10.62940/als.v13i3.3872

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