Development of transcriptomic biomarker signature in human saliva to detect lung cancer

Cell Mol Life Sci. 2012 Oct;69(19):3341-3350. doi: 10.1007/s00018-012-1027-0. Epub 2012 Jun 12.

Abstract

Lung cancer is the leading cause of cancer death for both men and women worldwide. Since most of the symptoms found for lung cancer are nonspecific, diagnosis is mostly done at late and progressed stage with the consecutive poor therapy outcome. Effective early detection techniques are sorely needed. The emerging field of salivary diagnostics could provide scientifically credible, easy-to-use, non-invasive and cost-effective detection methods. Recent advances have allowed us to develop discriminatory salivary biomarkers for a variety of diseases from oral to systematic diseases. In this study, salivary transcriptomes of lung cancer patients were profiled and led to the discovery and pre-validation of seven highly discriminatory transcriptomic salivary biomarkers (BRAF, CCNI, EGRF, FGF19, FRS2, GREB1, and LZTS1). The logistic regression model combining five of the mRNA biomarkers (CCNI, EGFR, FGF19, FRS2, and GREB1) could differentiate lung cancer patients from normal control subjects, yielding AUC value of 0.925 with 93.75 % sensitivity and 82.81 % specificity in the pre-validation sample set. These salivary mRNA biomarkers possess the discriminatory power for the detection of lung cancer. This report provides the proof of concept of salivary biomarkers for the non-invasive detection of the systematic disease. These results poised the salivary biomarkers for the initiation of a multi-center validation in a definitive clinical context.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Aged
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Cysteine-Rich Protein 61 / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Fibroblast Growth Factors / genetics
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Predictive Value of Tests
  • Proto-Oncogene Proteins B-raf / genetics
  • Regression Analysis
  • Saliva / physiology*
  • Smoking
  • Transcriptome
  • Tumor Suppressor Proteins / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • CCN1 protein, human
  • Cysteine-Rich Protein 61
  • DNA-Binding Proteins
  • FGF19 protein, human
  • FRS2 protein, human
  • GREB1 protein, human
  • LZTS1 protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • Tumor Suppressor Proteins
  • Fibroblast Growth Factors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf