Development and validation of a potential salivary biomarker panel for Oral Squamous Cell Carcinoma

Abstract

AbstractPurposeOral Squamous Cell Carcinoma (OSCC) is one of the most prevalent cancers in the world with maximum number of cases reported from India. Poor survival rate associated with OSCC can be attributed to non-availability of a biomarker, as one of the major reasons, leading to late presentation. Identification of an early diagnostic biomarker, which can also be used as a screening tool, will be helpful in reducing the disease morbidity and mortality.Experimental DesignIn this article we report Parallel Reaction Monitoring (PRM) based validation of 12 candidate proteins, identified initially by TMT tag based relative quantification of salivary proteins on LC-MS, in the saliva of Oral Squamous Cell Carcinoma (OSCC) cases (N=50) and healthy controls (N=49), AZGP1, AHSG, KRT6C, S100A7, S100A9, KLK1, BPIFB2, IGLL5, CORO1A, LACRT, LCN2 and PSAP. Heavy isotope labelled reference peptides were used to produce calibration curve and absolute quantification of proteins and resulting data was analyzed statistically using R.ResultsSalivary AHSG (p=0.0041**) and KRT6C (p=0.002**) were significantly upregulated in OSCC cases while AZGP1 (p=<0.0001***), KLK1 (p=0.006**) and BPIFB2 (p=0.0061**) were significantly downregulated. Multivariate logistic regression modelling resulted in a risk prediction model consisting of AZGP1, AHSG and KRT6C with p value <0.0001***. Using this model ROC with area under the curve of 82.2% was produced and sensitivity and specificity observed for this model was 78% and 73.5%. Positive and negative predictive values for the model were 76% and 75% respectively.ConclusionWe report a potential biomarker panel consisting of proteins AZGP1, AHSG and KRT6C for early diagnosis of OSCC.