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Peer-reviewedCC BYFrontiers in bioinformatics

Profiling the MMP family genes as prognostic biomarkers in oral squamous cell carcinoma: from computational discovery to clinical validation in a South Indian cohort

  1. 1School of Bio Sciences and Technology, Vellore Institute of Technology , , ,
  2. 2Department of Surgical Oncology, Center for Oncology, Government Royapettah Hospital , , ,

Abstract

Background: Over the past decade, lifestyle-related habits and environmental exposures have substantially increased the global incidence of Oral squamous cell carcinoma (OSCC). This trend underscores the importance of early screening to improve patient treatment outcomes, as delayed diagnosis severely reduces survival chances. Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent proteolytic enzymes that degrade the components of extracellular matrix, thereby promoting tumor progression, invasion and metastasis. Despite their well-established roles in OSCC, the overall clinical relevance of MMPs remains unclear.

Methods: This study systematically investigates the transcriptional expression landscape of all 23 human MMPs to determine their prognostic relevance in OSCC. Through an integrated analysis of the Gene Expression Omnibus and The Cancer Genome Atlas databases, six overlapping differentially expressed genes of MMP family were identified from the human oral tissue transcriptomic datasets. Prognostic relevance of these MMPs were examined by receiver operating characteristic curves, survival analyses, and predictive nomograms.

Results: Computational analysis revealed that the prediction model achieved optimal accuracy when the six selected MMPs (MMP-1, MMP-10, MMP-3, MMP-12, MMP-13, and MMP-9) were combined with Tumor-Node-Metastasis staging system. Gene Set Enrichment Analysis demonstrated that the MMPs were associated with metabolic reprogramming and proliferation-related signaling pathways, highlighting their contribution towards oral tumor progression. To validate the in silico transcriptomic findings, we performed an enzyme-linked immunosorbent assay to quantify the serum levels of MMP-1, MMP-10, and MMP-9 in South Indian OSCC patients. These proteins were significantly elevated in OSCC patients than healthy control samples (p < 0.0001, p < 0.0001 and p = 0.0002) respectively.

Conclusion: This study reveals that the elevated serum levels of MMP-1, MMP- 10 and MMP-9 can serve as minimally invasive prognostic biomarkers for OSCC in the South Indian cohort.

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BibTeX
@article{subhashini2026profiling,
  title = {{Profiling the MMP family genes as prognostic biomarkers in oral squamous cell carcinoma: from computational discovery to clinical validation in a South Indian cohort}},
  author = {P. Sakthi Subhashini and T. Bharanidharan and D. Suresh Kumar and S. Asha Devi},
  journal = {Frontiers in bioinformatics},
  year = {2026},
  month = oct,
  doi = {10.3389/fbinf.2026.1955795},
  url = {https://europepmc.org/article/PMC/PMC13719550},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Profiling the MMP family genes as prognostic biomarkers in oral squamous cell carcinoma: from computational discovery to clinical validation in a South Indian cohort
AU  - P. Sakthi Subhashini
AU  - T. Bharanidharan
AU  - D. Suresh Kumar
AU  - S. Asha Devi
PY  - 2026
DA  - 2026/10/16
JO  - Frontiers in bioinformatics
DO  - 10.3389/fbinf.2026.1955795
UR  - https://europepmc.org/article/PMC/PMC13719550
AB  - Background: Over the past decade, lifestyle-related habits and environmental exposures have substantially increased the global incidence of Oral squamous cell carcinoma (OSCC). This trend underscores the importance of early screening to improve patient treatment outcomes, as delayed diagnosis severely reduces survival chances. Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent proteolytic enzymes that degrade the components of extracellular matrix, thereby promoting tumor progression, invasion and metastasis. Despite their well-established roles in OSCC, the overall clinical relevance of MMPs remains unclear.  Methods: This study systematically investigates the transcriptional expression landscape of all 23 human MMPs to determine their prognostic relevance in OSCC. Through an integrated analysis of the Gene Expression Omnibus and The Cancer Genome Atlas databases, six overlapping differentially expressed genes of MMP family were identified from the human oral tissue transcriptomic datasets. Prognostic relevance of these MMPs were examined by receiver operating characteristic curves, survival analyses, and predictive nomograms.  Results: Computational analysis revealed that the prediction model achieved optimal accuracy when the six selected MMPs (MMP-1, MMP-10, MMP-3, MMP-12, MMP-13, and MMP-9) were combined with Tumor-Node-Metastasis staging system. Gene Set Enrichment Analysis demonstrated that the MMPs were associated with metabolic reprogramming and proliferation-related signaling pathways, highlighting their contribution towards oral tumor progression. To validate the in silico transcriptomic findings, we performed an enzyme-linked immunosorbent assay to quantify the serum levels of MMP-1, MMP-10, and MMP-9 in South Indian OSCC patients. These proteins were significantly elevated in OSCC patients than healthy control samples (p < 0.0001, p < 0.0001 and p = 0.0002) respectively.  Conclusion: This study reveals that the elevated serum levels of MMP-1, MMP- 10 and MMP-9 can serve as minimally invasive prognostic biomarkers for OSCC in the South Indian cohort.
SN  - 2673-7647
ER  -