Functional stratification of biomarkers selected from microarray data for understanding oral leukoplakia associated carcinogenesis

Oral carcinogenesis, a multistep phenomenon often precedes by oral pre-cancers like leukoplakia (OLK). Differentially expressed (DE) gene analysis of microarray data followed by functional classification provides an idea of alteration of biological functions associated with disease progression. In this context, microRNA (miRNA) microarray data analysis for functional classification is still a challenge, since most of the functions of miRNAs are yet to be discovered. The rationale of this study is to identify a subset of miRNA from microarray data, efficiency of which were evaluated using support vector machine for optimal supervised classification of OLK and OLK transformed oral squamous cell carcinoma (LK-OSCC). Another study was performed to identify subset of DE genes from gene expression database for OLK and LK-OSCC differentiation. This study further considered functional classification of target genes of DE miRNAs and DE genes and compared to understand OLK associated carcinogenesis mechanism, which is first of its kind. Result suggested that group of eight DE miRNAs, viz. miR-21, miR-142-3p, mir-223, miR-637, miR-142-5p, miR-1184 and miR-31* could classify OLK and LK-OSCC with 100% sensitivity and specificity. During comparative assessment of functionally classified target genes of DE miRNAs and mRNAs, it was observed that beside few common functional gene sets, the exclusive DE genes in miRNA target gene groups were TBC1 domain family and kinesin family while histone clusters, WD repeat domain genes, ribosomal proteins, transmembrane proteins and olfactory related proteins were significant in DE genes. Pathway analysis of the DE genes mainly showed to affect pathways especially for glutathione, drug and tyrosine metabolism as well as melanogenesis. The significant biological processes found to be affected by gene ontology analysis were mainly the response to lipid peroxide and altered secondary metabolite and melanin biosynthesis.