Genome-wide analysis of gene expression in Normal oral mucosa and different stages of oral submucous fibrosis. Homo sapiens

Analysis of various of up-regulated and down-regulated genes in normal oral mucosa and different stages of OSF. The report provides a data analysis methodology for identification of co-expressed gene patterns, as emerging clusters, in global transcriptome of oral mucosal pre-malignant and malignant conditions in comparison to their normal counterparts. Microarray based study of global gene expression is often used to extract molecular signatures underlying cancer progression. Such endeavors endorse self organizing map, a type of artificial neural network to analyze high dimensional pre-processed transcriptome data to segregate hotspot genes in component plane for disease subtypes. This report provides a data analysis methodology for identification of co-expressed gene patterns, as emerging clusters, in global transcriptome of oral mucosal pre-malignant and malignant conditions in comparison to their normal counterparts. Four exclusive cluster patterns, each involving 100 − 300 genes, were identified from component planes for oral study groups. Gene expression associated with each pattern belonged to 32 biological processes. The transcription and RNA processing, and angiogenesis were dominant in normal oral condition, while immunity, cellular differentiation and migration, neuron signalling, connective tissue organization, tumor suppression, and enzyme regulation showed predominance in oral squamous cell carcinoma. In dysplasia skeletal and ligament development processes were dominant while in non-dysplastic sub-mucous fibrosis cytoskeleton reorganization and neuron signalling were pre-dominant. In dysplasia an intermediate pattern with nine different dominant functional processes was identified. This analysis demonstrated utility of self organizing map to capture dominant enriched patterns as visual plots and revealed six common biological processes like transcription and RNA processing, cytoskeleton reorganization, angiogenesis, immunity, neuron signalling, and connective tissue remodeling in the pathogenesis of oral cancer. In fact it could provide an intuitive understanding of molecular course in carcinogenesis and may contribute for combinatorial biomarker discovery. Overall design: Oral submucous fibrosis (OSF) is one of the potential premalignant condition with high prevalence (0.3 − 3.2%) in South-Asian population . Clinically, OSF patient exhibit marked rigidity of oral mucosa and trismus. OSF is frequently accompanied by different grades of epithelial dysplasia which contributes to the high rate of malignant transformation (7 − 13%). Incisional biopsies from Oral submucous Fibrosis (OSF) and OSF associated squamous cell carcinoma (OSCC) were collected. All the collected biopsies were divided into two and one half was processed for the purpose of light microscopy evaluation. After histopathological confirmation of disease condition by onco-pathologist, the other half of the tissue was used for microarray analysis. The normal oral mucosa (NOM) samples were used as control. NOM samples were collected from individuals suffering from impacted mandibular third molar teeth and were in need of trans-alveolar extraction. The excess amount of muco-periosteal buccal flaps that has been left after trans alveolar surgeries have been excised and used as normal sample. The aim of the study is to investigate the differential transcrptomics modulations that are responsible for the transition of normal oral mucosa to premalinant disorders and later its malignant transformation to cancer.