Serum exosome-derived biomarkers for the early detection of oral squamous cell carcinoma

Mol Cell Biochem. 2021 Dec;476(12):4435-4447. doi: 10.1007/s11010-021-04254-7. Epub 2021 Sep 1.

Abstract

Blood exosomes help regulate communication between tumour cells, moderating their behaviour. We sought to determine the protein content in serum exosomes (SEs), to characterise SEs, and to discover novel clinical biomarkers of oral squamous cell carcinoma (OSCC). Differentially expressed proteins (DEPs) of OSCC were identified using proteomics and then analysed using bioinformatics, before validation using ELISA, IHC, and RT-PCR. The influence of SEs on oral cancer cells was detected using CCK-8 and migration assays. Twelve DEPs were found in SEs from OSCC. Four proteins were targeted for further verification. New biomarkers exhibiting high sensitivity and specificity in diagnosing OSCC comprised C-reactive protein (CRP), von willebrand factor (VWF), and leucine-rich alpha-2-glycoprotein (LRG). Combined biomarkers outperformed any single protein. We also demonstrated that tumour-derived exosomes promoted tumour cell migration, but not proliferation and apoptosis. Our study indicates that CRP, VWF, and LRG are potential clinically relevant OSCC biomarkers. OSCC-related SEs may help promote migration of oral cells.

Keywords: Biomarkers; Migration; Oral squamous cell carcinoma; Serum exosomes.

MeSH terms

  • Biomarkers, Tumor / blood
  • C-Reactive Protein / metabolism*
  • Early Detection of Cancer / methods
  • Exosomes / metabolism*
  • Glycoproteins / metabolism*
  • Head and Neck Neoplasms / blood
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / metabolism
  • Humans
  • Proteomics / methods
  • ROC Curve
  • Squamous Cell Carcinoma of Head and Neck / blood
  • Squamous Cell Carcinoma of Head and Neck / diagnosis*
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • von Willebrand Factor / metabolism*

Substances

  • Biomarkers, Tumor
  • Glycoproteins
  • LRG1 protein, human
  • von Willebrand Factor
  • C-Reactive Protein