Identification of candidate biomarkers that involved in the epigenetic transcriptional regulation for detection gastric cancer by iTRAQ based quantitative proteomic analysis

Abstract

Background: The sensitivities and specificities of biomarkers for gastric cancer are insufficient for clinical detection, and new diagnostics are therefore urgently required.

Methods: A discovery set of gastric cancer tissues was labeled with iTRAQ reagents, separated using SCX chromatography, and identified using LC-ESI-MS/MS. A validation set of gastric cancer tissues was used to confirm the expression levels of potential markers.

Results: The present study detected metastasis-associated protein 2 (MTA2) and Histone deacetylases 1 (HDAC1) proteins that were overexpressed in gastric cancer tissues compared with that in adjacent gastric tissue. The sensitivity and specificity of MTA2 in detecting 76 cases gastric cancers were 57.9% (95% CI: 46.5%-69.3%) and 55.3% (95% CI: 43.8%-66.7%), respectively. The sensitivity and specificity of HDAC1 were 61.8% (95% CI: 50.7%-73%) and 63.2% (95% CI: 52.1%-74.3%), respectively. The co-expression of MTA2 and HDAC1 in gastric cancer achieved 65.3% sensitivity (95% CI: 51.5%-79.1%) and 65.2% specificity (95% CI: 50.9%-79.5%), which was strongly associated with lymph node metastasis and TNM staging.

Conclusion: The present findings indicated a tight correlation between the MTA2 and HDAC1 expression level and lymph node metastasis and TNM staging in gastric cancers. Therefore, MTA2 and HDAC1 might be predictors of lymph node metastasis phenotype and possible target molecule for anticancer drug design in human gastric cancer.

Keywords: Epigenetic; Gastric cancer; HDAC1; MS/MS; MTA2; iTRAQ.