Elucidating drivers of oral epithelial dysplasia formation and malignant transformation to cancer using RNAseq

Abstract

Oral squamous cell carcinoma (OSCC) is a prevalent cancer with poor prognosis. Most OSCC progresses via a non-malignant stage called dysplasia. Effective treatment of dysplasia prior to potential malignant transformation is an unmet clinical need. To identify markers of early disease, we performed RNA sequencing of 19 matched HPV negative patient trios: normal oral mucosa, dysplasia and associated OSCC. We performed differential gene expression, principal component and correlated gene network analysis using these data. We found differences in the immune cell signatures present at different disease stages and were able to distinguish early events in pathogenesis, such as upregulation of many HOX genes, from later events, such as down-regulation of adherens junctions. We herein highlight novel coding and non-coding candidates for involvement in oral dysplasia development and malignant transformation, and speculate on how our findings may guide further translational research into the treatment of oral dysplasia.

Pathway based prognostic gene expression profile of buccal and gingivo‐buccal oral squamous cell carcinoma in smokeless tobacco chewers

“…The accumulation of somatic mutations in genes and molecular pathways is a major factor in the development of OSCC. Whole transcriptome sequencing (RNA‐Seq) is a superior approach which enables detection of somatic mutations and gene expression of coding and noncoding RNA; simultaneously …”

“…Chronic inflammation may represent a potential common denominator in development of OSCC . Microarray analysis of gene expression in OSCC cell lines with high basal NF‐KB activity and patients with OSCC samples identified dysregulation of many genes involved in inflammation, wound healing, angiogenesis, and growth regulation.…”

“…Whole transcriptome sequencing (RNA-Seq) is a superior approach which enables detection of somatic mutations and gene expression of coding and noncoding RNA; simultaneously. 13,14 A study was undertaken to determine the gene expression profile of OSCC caused due to chewing tobacco affecting the BM and GB region of the oral cavity. Also, we wanted to assess if there was any difference in the genetic profile of OSCC occurring in these two subsites (OSCC-BM and OSCC-GB) of the oral cavity, which could serve as diagnostic/prognostic indicators.…”

How to analyse the spatiotemporal tumour samples needed to investigate cancer evolution: A case study using paired primary and recurrent glioblastoma

“…All bam files underwent base recalibration and indel realignment (GATK v3.4–46) . RNAseq data was processed as previously described …”

Immune checkpoints indoleamine 2,3‐dioxygenase 1 and programmed death‐ligand 1 in oral mucosal dysplasia

“…However, several studies showed a wide range (5%‐27%) of transformation risks, mainly depending on dysplasia grade . It is believed that during malignant transformation, the dysplastic cells may escape from destruction mediated by the adaptive immune system …”