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Background <p>Matrix metalloproteinases (MMPs) are the endopeptidase enzymes that are involved in the degradation of the extracellular matrix which is the hallmark of metastasis. Oral cancer is one of the most prevalent cancers in India which have poor survival outcomes primarily due to the metastasis and recurrence of disease. Previous studies have analyzed the concentration of MMPs in various body fluids and tissue samples, but limited data is available on MMPs enzyme activity.</p> Objective <p>The present study aims to analyze the prognostic value of MMPs enzyme activity in oral cancer patients using the fluorogenic peptide substrate assay. We aim to correlate the MMPs enzyme activity level with overall and disease-free survival. We work towards calculating the cutoff values for MMPs enzyme activity to predict survival or mortality over two years of follow-up. At last, we develop a regression equation to estimate the survival duration in oral cancer patients based on MMPs enzyme activity.</p> Methods <p>The present study involved total 46 oral cancer patients who were followed up for two years. The MMPs activity was analyzed at baseline and after two years of follow-up. We also included 14 healthy individuals in which MMPs activity was analyzed as a control group. Fluorogenic peptide substrate assay was used to analyze the activity of various MMPs (MMP-1, 2, 7, 8, 9, 12, 13, 14, 15 and MMP-16). Sociodemographic and clinical data of patients was also captured using a predesigned proforma. Over the follow-up of two years, overall survival duration, disease-free survival duration, mortality, treatment relapse or recurrence was recorded and correlated with the MMPs enzyme activity.</p> Results <p>The mean age of the oral cancer patients was 50.41 ± 13.62 years, with a male predominance (73.9%). Patients with alveolar cancer demonstrated significantly higher MMP enzymatic activity compared with other oral subsites. Although baseline MMP activity was higher in oral cancer patients than in healthy controls and showed a reduction after two years of follow-up, these differences did not reach statistical significance. Over the two-year follow-up period, the mortality rate was 45.7% and the recurrence rate was 10.9%. MMP enzymatic activity was numerically higher among patients who died compared with survivors; however, this difference was not statistically significant. A negative correlation was observed between baseline MMP activity and disease-free survival, though this association was also non-significant. ROC analysis demonstrated only modest discriminatory ability for mortality and no discriminatory ability for recurrence.</p> Conclusion <p>Matrix metalloproteinases play an important role in disease progression, and the present study suggests that active MMP enzymatic activity may have preliminary prognostic relevance in oral cancer. Although oral cancer patients exhibited higher MMP activity compared with healthy individuals, the difference was not statistically significant. All findings should be interpreted cautiously, given the modest sample size, limited outcome events, and use of unmatched healthy controls. The results are exploratory and hypothesis-generating in nature. Larger, well-matched, multicentric studies with adequate power are required to validate the potential prognostic utility of active MMP enzymatic activity and to clarify its role in survival assessment.</p>

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Active Matrix Metalloproteinase Profiling in Oral Cancer Using Fluorogenic Peptide Substrate Assays

  • 期刊论文

  • 发表日期：

    2026年4月2日

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  • Jyoti Saini,
  • Dawood Agoo,
  • Varnika Punia,
  • Jaimanti Bakshi,
  • Maryada Sharma,
  • Atul Kumar Goyal

摘要

Background

Matrix metalloproteinases (MMPs) are the endopeptidase enzymes that are involved in the degradation of the extracellular matrix which is the hallmark of metastasis. Oral cancer is one of the most prevalent cancers in India which have poor survival outcomes primarily due to the metastasis and recurrence of disease. Previous studies have analyzed the concentration of MMPs in various body fluids and tissue samples, but limited data is available on MMPs enzyme activity.

Objective

The present study aims to analyze the prognostic value of MMPs enzyme activity in oral cancer patients using the fluorogenic peptide substrate assay. We aim to correlate the MMPs enzyme activity level with overall and disease-free survival. We work towards calculating the cutoff values for MMPs enzyme activity to predict survival or mortality over two years of follow-up. At last, we develop a regression equation to estimate the survival duration in oral cancer patients based on MMPs enzyme activity.

Methods

The present study involved total 46 oral cancer patients who were followed up for two years. The MMPs activity was analyzed at baseline and after two years of follow-up. We also included 14 healthy individuals in which MMPs activity was analyzed as a control group. Fluorogenic peptide substrate assay was used to analyze the activity of various MMPs (MMP-1, 2, 7, 8, 9, 12, 13, 14, 15 and MMP-16). Sociodemographic and clinical data of patients was also captured using a predesigned proforma. Over the follow-up of two years, overall survival duration, disease-free survival duration, mortality, treatment relapse or recurrence was recorded and correlated with the MMPs enzyme activity.

Results

The mean age of the oral cancer patients was 50.41 ± 13.62 years, with a male predominance (73.9%). Patients with alveolar cancer demonstrated significantly higher MMP enzymatic activity compared with other oral subsites. Although baseline MMP activity was higher in oral cancer patients than in healthy controls and showed a reduction after two years of follow-up, these differences did not reach statistical significance. Over the two-year follow-up period, the mortality rate was 45.7% and the recurrence rate was 10.9%. MMP enzymatic activity was numerically higher among patients who died compared with survivors; however, this difference was not statistically significant. A negative correlation was observed between baseline MMP activity and disease-free survival, though this association was also non-significant. ROC analysis demonstrated only modest discriminatory ability for mortality and no discriminatory ability for recurrence.

Conclusion

Matrix metalloproteinases play an important role in disease progression, and the present study suggests that active MMP enzymatic activity may have preliminary prognostic relevance in oral cancer. Although oral cancer patients exhibited higher MMP activity compared with healthy individuals, the difference was not statistically significant. All findings should be interpreted cautiously, given the modest sample size, limited outcome events, and use of unmatched healthy controls. The results are exploratory and hypothesis-generating in nature. Larger, well-matched, multicentric studies with adequate power are required to validate the potential prognostic utility of active MMP enzymatic activity and to clarify its role in survival assessment.