Comparative proteomics of oral squamous cell carcinoma tissue in consumers and non-consumers of tobacco

Tobacco is a risk factor for oral squamous cell carcinoma (OSCC). Some cases of OSCC occur without any known cause and is called idiopathic OSCC. Understanding proteomic signatures in tissues of patients in these two groups is crucial for understanding etio-pathogenic pathways involved in cancer causation.

Five biopsy tissue samples, each from ulcero-proliferative growth of histopathologically proven squamous cell carcinoma, were taken from habitual tobacco consumers and non-tobacco consumers. Proteins were extracted, reduced, alkylated, trypsin digested, and desalted using C18 column. Label-free proteomics was carried out by subjecting 1 µg of peptides from each of the samples to mass spectrometric analysis on an Orbitrap Exploris 240 using data-dependent acquisition mode. Raw files were processed using Proteome Discoverer (v2.4), and differentially expressed proteins were normalized and identified using Shiny Protigy (v1.1.7). Principal component analysis was performed using ClustVis to look for variance between the two groups. String App plugin in Cytoscape version 3.10.0 was employed to construct a comprehensive interaction network for the differentially expressed proteins.

828 proteins were identified in all samples. Proteins SGT1 homolog, eukaryotic translation initiation factor 4H, small ribosomal subunit protein Es1, and stromal interaction molecule—isoform of Q13586 were upregulated in cancer tissues of tobacco consumers, while dihydropyrimidinase-related protein 2, peptidyl-prolyl cis–trans isomerase, tetraspanin (CD63), and cytochrome C were upregulated in cancer tissues of non-tobacco consumers. Two clinical phenotypes were distinctly segregated based on differential expression of these proteins.

There are differentially expressed proteins in oral cavity tissues of tobacco users and non-tobacco users. These proteins are implicated in causation of cancer by distinct pathways in the two phenotypes.