Diagnostic power of VEGF, MMP-9 and TIMP-1 in patients with breast cancer. A multivariate statistical analysis with ROC curve

Adv Med Sci. 2019 Mar;64(1):1-8. doi: 10.1016/j.advms.2018.07.002. Epub 2018 Sep 15.

Abstract

Purpose: Vascular endothelial growth factor is an important factor in promoting angiogenesis in malignant processes, matrix metalloproteinase-9 in the degradation of extracellular matrix, which enhances metastasis, and tissue inhibitor of metalloproteinase-1 is its inhibitor. The aim of this study was to investigate the diagnostic power of these parameters in comparison to CA15-3 in breast cancer patients and in relation to the control group.

Materials/methods: The study included 120 breast cancer patients, 60 patients with benign breast tumors and 60 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA15-3 by chemiluminescent microparticle immuno assay.

Results: Tissue inhibitor of metalloproteinase-1 showed the highest value of sensitivity in breast cancer group (86.25%) and, more importantly, highest value in breast cancer stage I (85%). Vascular endothelial growth factor also showed high sensitivity (stage I and II-75%, III-85%, IV-70% and 76.25% in total breast cancer group) and the highest specificity (85%) from all tested parameters. It was also the only parameter which had statistically significant area under curve in all stages. In the total breast cancer group all tested parameters showed statistically significant area under curve, but the maximum range was obtained for combination: 'vascular endothelial growth factor + CA15-3'. Vascular endothelial growth factor seems to be the best candidate for diagnosing breast cancer stage I and for differentiating between breast cancer and non-carcinoma cases.

Conclusions: The combined analysis of tested parameters and CA15-3 resulted in an increase in sensitivity and area under curve values, which provides hope for developing new panel of biomarkers that may be used in diagnosing breast cancer in the future.

Keywords: Area under curve; New biomarkers panel; ROC; Tumor markers.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / blood*
  • Breast Neoplasms / diagnosis*
  • Case-Control Studies
  • Female
  • Humans
  • Matrix Metalloproteinase 9 / blood*
  • Middle Aged
  • Mucin-1 / blood
  • Multivariate Analysis
  • ROC Curve
  • Sensitivity and Specificity
  • Tissue Inhibitor of Metalloproteinase-1 / blood*
  • Vascular Endothelial Growth Factor A / blood*

Substances

  • Mucin-1
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 9