Discovery of potential serum protein biomarkers for lymph node metastasis in oral cancer

Head Neck. 2016 Jan;38(1):118-25. doi: 10.1002/hed.23870. Epub 2015 Jun 25.

Abstract

Background: The purpose of our study was to identify serum protein biomarkers for node-positive oral squamous cell carcinoma (OSCC). Biomarkers indicating lymph node metastasis provides a valuable classification methodology to optimize treatment plans for patients with OSCC.

Methods: Quantitative serum proteomic analysis of OSCCs with either node-positive or node-negative disease was performed with tandem mass spectrometry and isobaric tagging for relative and absolute quantitation (iTRAQ). Immunoassays were used to validate a panel of candidate protein biomarkers and receiver operating characteristic (ROC) analysis was used to evaluate the performance of the candidate biomarkers.

Results: A total of 282 serum proteins were quantified between node-positive and node-negative OSCCs with the proteomic approach. Four candidate biomarkers, gelsolin, fibronectin, angiotensinogen, and haptoglobin, were validated in an independent group of patients with node-positive or node-negative OSCC. The best candidate biomarker, gelsolin, yielded a ROC value of 89% for node-positive OSCC, although the sample size for validation is relatively small. Fibronectin, gelsolin, and angiotensinogen were also found to be differentially expressed between cancer cell lines of node-positive and node-negative cancer origin.

Conclusion: Our studies suggest that testing of serum protein biomarkers might help detect lymph node metastasis of oral cancer. Because of limited sample size in our studies, long-term longitudinal studies with large populations of individuals with oral cancer are needed to validate these potential biomarkers.

Keywords: lymph node metastasis; oral cancer; quantitative proteomics; serum biomarker.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Angiotensinogen / blood*
  • Biomarkers, Tumor / blood*
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics*
  • Female
  • Fibronectins / blood*
  • Gelsolin / blood*
  • Haptoglobins / metabolism*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mouth Neoplasms / blood
  • Mouth Neoplasms / diagnosis
  • Mouth Neoplasms / genetics*
  • Predictive Value of Tests
  • Sensitivity and Specificity
  • Serine Proteinase Inhibitors / blood

Substances

  • Biomarkers, Tumor
  • Fibronectins
  • Gelsolin
  • Haptoglobins
  • Serine Proteinase Inhibitors
  • Angiotensinogen