title: 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.
authors.affiliation: Precancer Genomics, Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, LS9 7TF, UK.|Stratified Medicine (Oncology), School of Biomedical Sciences, University of Ulster, Coleraine, Co. Londonderry, BT52 1SA, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Conway
authors.affiliation: Precancer Genomics, Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, LS9 7TF, UK.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Graham
authors.affiliation: Precancer Genomics, Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, LS9 7TF, UK.
authors.forename: Preetha
authors.initials: P
authors.lastname: Chengot
authors.affiliation: Precancer Genomics, Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, LS9 7TF, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Daly
authors.affiliation: Precancer Genomics, Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, LS9 7TF, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Chalkley
authors.affiliation: Precancer Genomics, Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, LS9 7TF, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Ross
authors.affiliation: Precancer Genomics, Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, LS9 7TF, UK.
authors.forename: Alastair
authors.initials: A
authors.lastname: Droop
authors.affiliation: Precancer Genomics, Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, LS9 7TF, UK.
authors.forename: Pamela
authors.initials: P
authors.lastname: Rabbitts
authors.affiliation: Precancer Genomics, Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, LS9 7TF, UK.
authors.forename: Lucy F
authors.initials: LF
authors.lastname: Stead
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016000:Cluster Analysis; D003937:Diagnosis, Differential; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000235:genetics*; D011230:Precancerous Conditions / Q000175:diagnosis / Q000235:genetics*; D025341:Principal Component Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017423:Sequence Analysis, RNA / Q000379:methods*
keywords: OSCC; RNAseq; dysplasia; non-coding; oral squamous cell carcinoma