Identification of Salivary Biomarkers for Oral Cancer Detection with Untargeted and Targeted Quantitative Proteomics Approaches

Mol Cell Proteomics. 2019 Sep;18(9):1796-1806. doi: 10.1074/mcp.RA119.001530. Epub 2019 Jun 28.

Abstract

Oral cavity squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. In Taiwan, OSCC is the fifth leading cause of cancer-related mortality and leads to 2800 deaths per year. The poor outcome of OSCC patients is principally ascribed to the fact that this disease is often advanced at the time of diagnosis, suggesting that early detection of OSCC is urgently needed. Analysis of cancer-related body fluids is one promising approach to identify biomarker candidates of cancers. To identify OSCC biomarkers, salivary proteomes of OSCC patients, individuals with oral potentially malignant disorders (OPMDs), and healthy volunteers were comparatively profiled with isobaric tags for relative and absolute quantitation (iTRAQ)-based mass spectrometry (MS). The salivary levels of 67 and 18 proteins in the OSCC group are elevated and decreased compared with that in the noncancerous group (OPMD and healthy groups), respectively. The candidate biomarkers were further selected using the multiple reaction monitoring (MRM)-MS and validated with the immunoassays. More importantly, the higher salivary level of three proteins, complement factor H (CFH), fibrinogen alpha chain (FGA), and alpha-1-antitrypsin (SERPINA1) was correlated with advanced stages of OSCC. Our results indicate that analysis of salivary proteome is a feasible strategy for biomarker discovery, and the three proteins are potential salivary markers for OSCC diagnosis.

Keywords: Biomarker: Diagnostic; Biomarker: Prognostic; Cancer biomarker(s); Head and neck cancer; Multiple reaction monitoring; Oral cavity squamous cell carcinoma; Oral potentially malignant disorder; iTRAQ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Case-Control Studies
  • Complement Factor H / analysis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibrinogen / analysis
  • Humans
  • Limit of Detection
  • Male
  • Mass Spectrometry / methods
  • Middle Aged
  • Mouth Neoplasms / diagnosis*
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / mortality
  • Precancerous Conditions / metabolism
  • Prognosis
  • Proteomics / methods
  • Reproducibility of Results
  • Saliva / chemistry*
  • Sensitivity and Specificity
  • alpha 1-Antitrypsin / analysis

Substances

  • Biomarkers, Tumor
  • CFH protein, human
  • FGA protein, human
  • SERPINA1 protein, human
  • alpha 1-Antitrypsin
  • Complement Factor H
  • Fibrinogen