Overexpression of angiogenic factors and matrix metalloproteinases in the saliva of oral squamous cell carcinoma patients: potential non-invasive diagnostic and therapeutic biomarkers

BMC Cancer. 2022 May 11;22(1):530. doi: 10.1186/s12885-022-09630-0.

Abstract

Backgrounds: Salivary biomarkers hold huge potential for the non-invasive diagnosis of oral squamous cell carcinoma. Angiogenic factors and matrix-metalloproteinases (MMPs) are highly expressed in OSCC tissue, but their expression patterns in the saliva are unknown. This study aimed to analyze the levels of angiogenic factors and MMPs in tumor tissue and saliva of OSCC patients.

Methods: OSCC-tissue, adjacent normal tissue (ANT), saliva from OSCC patients, and healthy controls were obtained. The expression patterns of angiogenic factors and MMPs were analyzed by immunohistochemistry, protein chip array, and RT-qPCR.

Results: Results showed higher expression of ANG, ANG-2, HGF, PIGF, VEGF, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1, and TIMP-2 in OSCC-tissues compared to the ANT. Among the overexpressed markers in OSCC-tissues, HGF, VEGF, PIGF, PDGF-BB, MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, and TIMP-2 were significantly upregulated in the saliva of OSCC patients compared to healthy controls.

Conclusions: The levels of HGF, VEGF, PIGF, MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, and TIMP-2 were upregulated both in OSCC tissue and saliva of OSCC patients. Bioinformatic analysis revealed the correlation of these factors with patient survival and cancer functional states in head and neck cancer, indicating these factors as possible saliva-based non-invasive diagnostic/prognostic markers and therapeutic targets of OSCC.

Keywords: Angiogenic factors; Diagnostic markers; MMPs; Oral squamous cell carcinoma; Saliva.

MeSH terms

  • Biomarkers, Tumor* / metabolism
  • Humans
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 10 / metabolism
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinase 8 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mouth Neoplasms* / diagnosis
  • Mouth Neoplasms* / pathology
  • Placenta Growth Factor / metabolism
  • Saliva / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / diagnosis
  • Squamous Cell Carcinoma of Head and Neck* / pathology
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Biomarkers, Tumor
  • Vascular Endothelial Growth Factor A
  • Tissue Inhibitor of Metalloproteinase-2
  • Placenta Growth Factor
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 10
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1