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MMP14 and DDR2 are potential molecular markers for metastatic triple-negative breast cancer

Rabeah Al-Temaimi1, Rasheed Ahmad2, Fahd Al-Mulla2

  • 1Human Genetics Unit, Department of Pathology, College of Medicine, Kuwait University, P.O.Box 24923, 13110, Jabriya, Kuwait. Rabeah.altemaimi@ku.edu.kw.

Scientific Reports
|July 2, 2025
PubMed

Insights

Triple-negative breast cancer (TNBC) is aggressive. Researchers identified Discoidin domain receptor 2 (DDR2) and MMP14 as key protein markers that can help detect metastatic TNBC, paving the way for new immunotherapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunotherapy

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive cancer subtype with high metastatic potential.
  • Current research focuses on identifying distinct molecular targets for effective targeted therapeutics.
  • Understanding the molecular landscape of TNBC is crucial for developing novel treatment strategies.

Purpose of the Study:

  • To investigate the protein expression of matrix metalloproteinases (MMPs) and Discoidin domain receptor 2 (DDR2) in metastatic and non-metastatic TNBC.
  • To identify potential molecular targets for immunotherapy in TNBC.
  • To evaluate the potential of these markers in predicting TNBC metastasis.

Main Methods:

  • Utilized TNBC tissue microarrays for protein expression analysis.
  • Correlated the expression of MMPs (MMP1, MMP2, MMP3, MMP11, MMP12, MMP13, MMP14) and DDR2 with tumor grade and metastatic status.
  • Developed multi-marker models to predict metastatic TNBC from non-metastatic TNBC.

Main Results:

  • MMP1 expression inversely correlated with tumor grade, while MMP2, 3, 12, and 13 expression directly correlated with tumor grade.
  • Metastatic TNBC showed significant correlation with the expression of DDR2, MMP11, and MMP14.
  • A 3-marker model (DDR2, MMP2, MMP14) and an all-marker model demonstrated significant potential in classifying metastatic TNBC.

Conclusions:

  • MMP14 and DDR2 are proposed as potential molecular markers for detecting metastatic TNBC.
  • The findings support further investigation into targeted dual immunotherapies against MMP14 and DDR2 for TNBC treatment.
  • Identifying these markers could lead to improved diagnostic and therapeutic strategies for TNBC.
Keywords:
Discoidin domain receptor 2Matrix metalloproteinaseMetastaticTriple-negative breast cancer

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