Identification of potential salivary biomarker panels for oral squamous cell carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide with the maximum number of incidences and deaths reported from India. One of the major causes of poor survival rate associated with OSCC has been attributed to late presentation due to non-availability of a biomarker. Identification of early diagnostic biomarker will help in reducing the disease morbidity and mortality. We validated 12 salivary proteins using targeted proteomics, identified initially by relative quantification of salivary proteins on LC–MS, in OSCC patients and controls. Salivary AHSG (p = 0.0041**) and KRT6C (p = 0.002**) were upregulated in OSCC cases and AZGP1 (p ≤ 0.0001***), KLK1 (p = 0.006**) and BPIFB2 (p = 0.0061**) were downregulated. Regression modelling resulted in a significant risk prediction model (p < 0.0001***) consisting of AZGP1, AHSG and KRT6C for which ROC curve had AUC, sensitivity and specificity of 82.4%, 78% and 73.5% respectively for all OSCC cases and 87.9%, 87.5% and 73.5% respectively for late stage (T3/T4) OSCC. AZGP1, AHSG, KRT6C and BPIFB2 together resulted in ROC curve (p < 0.0001***) with AUC, sensitivity and specificity of 94%, 100% and 77.6% respectively for N0 cases while KRT6C and AZGP1 for N+ cases with ROC curve (p < 0.0001***) having AUC sensitivity and specificity of 76.8%, 73% and 69.4%. Our data aids in the identification of biomarker panels for the diagnosis of OSCC cases with a differential diagnosis between early and late-stage cases.

Salivary Biomarkers in Oral Squamous Cell Carcinoma: A Proteomic Overview

“…Initially, 93 proteins were found, and up to 30 overexpressed were selected, and CD44, S100A7, and S100P were significantly associated as putative candidates for the early phase of tumor progression [ 41 ]. Aiming to differentiate the early to the late phase of OSCC patients, more recently, Jain et al, individuated from saliva samples several proteins by LC-MS in oral squamocellular cell cancer and thereafter twelve were validated using targeted proteomics [ 42 ]. Among these, Alpha 2 Glycoprotein 1 (AZGP1), Alpha-2-Heremans-Schmid Glycoprotein (AHSG), Keratin 6C (KRT6C) and BPI fold-containing family B member 2 (BPIFB2) showed high sensitivity and specificity, suggesting theirs as a potential salivary biomarker of different stages of OSCC [ 43 ].…”

The prognostic value of immune-related genes AZGP1, SLCO5A1, and CTF1 in Uveal melanoma

“…In our data, AZGP1 was considered to have a significant impact on KIRC, KIRP, UCEC, and UVM prognosis, but it has been shown that AZGP1 could be a feasible candidate biomarker for colorectal cancer based on an analysis of the GSE21962, GSE24551, and GSE29638 datasets in the GEO(Gene Expression Omnibus) database ( 24 ). Patients with oral squamous cell carcinoma (OSCC) have low salivary levels of AZGP1 ( 25 )and low mRNA levels of AZGP1 in OSCC tumor tissues ( 26 ). The role of AZGP1 in inhibiting cell invasion and migration ( 27 , 28 ) suggests its correlation with poor disease response.…”

The Use of Salivary Levels of Matrix Metalloproteinases as an Adjuvant Method in the Early Diagnosis of Oral Squamous Cell Carcinoma: A Narrative Literature Review

“…However, a limitation of the use of salivary biomarkers is related to their reduced concentrations (100–1000 fold) compared to plasma, but this aspect is not particularly crucial in the detection of OSCC because these molecules are secreted locally in the proximity of the primary tumor [ 49 ]. On the other hand, the standardization of salivary tests requires high specificity and sensitivity of the selected molecules [ 50 ] in order to differentiate PMOLs and OSCC from other inflammatory conditions, such as gingivitis, periodontitis or infections that might affect the levels of salivary biomarkers [ 51 ]. The presence of inflammation could result in false-positive responses, reducing the diagnostic value of the biomarkers in PMOLs and OSCC.…”