Identification and Validation of Matrix Metalloproteinase Hub Genes As Potential Biomarkers for Skin Cutaneous Melanoma

Overview

Journal Front Oncol

Specialty Oncology

Date 2024 Nov 4

PMID 39493455

Authors

Zhongyi Zhang

Mei Zhao

Zubing Zhou

Xiaodan Ren

Yunliang He

Tao Shen

Hongping Zeng

Kai Li

Yong Zhang

Affiliations

Soon will be listed here.

Abstract

Objectives: The role of matrix metalloproteinases (MMPs) in Skin Cutaneous Melanoma (SKCM) development and progression is unclear so far. This comprehensive study delved into the intricate role of MMPs in SKCM development and progression.

Methods: RT-qPCR, bisulfite sequencing, and WES analyzed MMP gene expression, promoter methylation, and mutations in SKCM cell lines. TCGA datasets validated findings. DrugBank and molecular docking identified potential regulatory drugs, and cell line experiments confirmed the role of key MMP genes in tumorigenesis.

Results: Our findings unveiled significant up-regulation of MMP9, MMP12, MMP14, and MMP16, coupled with hypomethylation of their promoters in SKCM cell lines, implicating their involvement in disease progression. Mutational analysis highlighted a low frequency of mutations in these genes, indicating less involvement of mutations in the expression regulatory mechanisms. Prognostic assessments showcased a significant correlation between elevated expression of these genes and poor overall survival (OS) in SKCM patients. Additionally, functional experiments involving gene silencing revealed a potential impact on cellular proliferation, further emphasizing the significance of MMP9, MMP12, MMP14, and MMP16 in SKCM pathobiology.

Conclusion: This study identifies Estradiol and Calcitriol as potential drugs for modulating MMP expression in SKCM, highlighting MMP9, MMP12, MMP14, and MMP16 as key diagnostic and prognostic biomarkers.

Citing Articles

Comprehensive investigation of matrix metalloproteinases in skin cutaneous melanoma: diagnostic, prognostic, and therapeutic insights.

Wu L, Liu C, Hu W Sci Rep. 2025; 15(1):2152.

PMID: 39820824 PMC: 11739484. DOI: 10.1038/s41598-025-85887-2.

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