MMP12 is a Potential Predictive and Prognostic Biomarker of Various Cancers Including Lung Adenocarcinoma

Cancer Control. 2024 Jan-Dec:31:10732748241235468. doi: 10.1177/10732748241235468.

Abstract

Objective: This study sought to explore the clinical value of matrix metalloproteinases 12 (MMP12) in multiple cancers, including lung adenocarcinoma (LUAD).

Methods: Using >10,000 samples, this retrospective study demonstrated the first pan-cancer analysis of MMP12. The expression of MMP12 between cancer groups and their control groups was analyzed using Wilcoxon rank-sum tests. The clinical significance of MMP12 expression in multiple cancers was assessed using receiver operating characteristic curves, Kaplan-Meier curves, and univariate Cox analysis. A further LUAD-related analysis based on 4565 multi-center and in-house samples was performed to verify the findings regarding MMP12 in pan-cancer analysis partly.

Results: MMP12 mRNA is highly expressed in 13 cancers compared to their controls, and the MMP12 protein level is elevated in some of these cancers (e.g., colon adenocarcinoma) (P < .05). MMP12 expression makes it feasible to distinguish 21 cancer tissues from normal tissues (AUC = 0.86). A high MMP12 expression is a prognosis risk factor in eight cancers, such as adrenocortical carcinoma (hazard ratio >1, P < .05). The elevated MMP12 expression is also a prognosis protective factor in breast-invasive carcinoma and colon adenocarcinoma (hazard ratio <1, P < .05). Some pan-cancer findings regarding MMP12 are verified in LUAD-MMP12 expression is upregulated in LUAD at both the mRNA and protein levels (P < .05), has the potential to distinguish LUAD with considerable accuracy (AUC = .91), and plays a risk prognosis factor for patients with the disease (P < .05).

Conclusions: MMP12 is highly expressed in most cancers and may serve as a novel biomarker for the prediction and prognosis of numerous cancers.

Keywords: area under the curve; expression; immune microenvironment; prognosis; standardized mean difference.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma* / diagnosis
  • Adenocarcinoma* / genetics
  • Breast Neoplasms*
  • Colonic Neoplasms*
  • Female
  • Humans
  • Lung Neoplasms* / genetics
  • Matrix Metalloproteinase 12 / genetics
  • Prognosis
  • RNA, Messenger / genetics
  • Retrospective Studies

Substances

  • Matrix Metalloproteinase 12
  • RNA, Messenger
  • MMP12 protein, human