Relevance of matrix metalloproteases in non-small cell lung cancer diagnosis

BMC Cancer. 2017 Dec 5;17(1):823. doi: 10.1186/s12885-017-3842-z.

Abstract

Background: The need for novel biomarkers that could aid in non-small cell lung cancer (NSCLC) detection, together with the relevance of Matrix Metalloproteases (MMPs) -1, -2, -7, -9 and -10 in lung tumorigenesis, prompted us to assess the diagnostic usefulness of these MMPs and the Tissue Inhibitor of Metalloproteinase (TIMP) -1 in NSCLC patients.

Methods: Markers were evaluated in an initial study cohort (19 NSCLC cases and 19 healthy controls). Those that better performed were analyzed in a larger sample including patients with benign lung diseases. Serum MMPs and TIMP-1 were determined by multiplexed immunoassays. Logistic regression was employed for multivariate analysis of biomarker combinations.

Results: MMPs and TIMP-1 were elevated in the serum of NSCLC patients compared to healthy controls. MMP-1, -7 and -9 performed at best and were further evaluated in the sample including benign pathologies, corroborating the superiority of MMP-9 in NSCLC discrimination, also at early-stage NSCLC. The optimal diagnostic value was obtained with the model including MMP-9, gender, age and smoking history, that demonstrated an AUC of 0.787, 85.54% sensitivity and 64.89% specificity.

Conclusion: Our results suggest that MMP-9 is a potential biomarker for NSCLC diagnosis and its combined measurement with other biomarkers could improve NSCLC detection.

Keywords: Diagnosis; Matrix metalloproteases; Non-small cell lung cancer; Serum biomarkers.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Case-Control Studies
  • Female
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / diagnosis*
  • Male
  • Matrix Metalloproteinases, Secreted / blood*
  • Middle Aged
  • Tissue Inhibitor of Metalloproteinase-1 / blood
  • Young Adult

Substances

  • Biomarkers, Tumor
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinases, Secreted