title: Gene expression profiling signatures for the diagnosis and prevention of oral cavity carcinogenesis-genome-wide analysis using RNA-seq technology.
abstract: We compared the changes in global gene expression between an early stage (the termination of the carcinogen treatment and prior to the appearance of frank tumors) and a late stage (frank squamous cell carcinoma (SCC)) of tongue carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model of human oral cavity and esophageal squamous cell carcinoma. Gene ontology and pathway analyses show that increases in "cell cycle progression" and "degradation of basement membrane and ECM pathways" are early events during SCC carcinogenesis and that changes in these pathways are even greater in the actual tumors. Myc, NFκB complex (NFKB1/RELA), and FOS transcription networks are the major transcriptional networks induced in early stage tongue carcinogenesis. Decreases in metabolism pathways, such as in "tricarboxylic acid cycle" and "oxidative phosphorylation", occurred only in the squamous cell carcinomas and not in the early stages of carcinogenesis. We detected increases in ALDH1A3, PTGS2, and KRT1 transcripts in both the early and late stages of carcinogenesis. The identification of the transcripts and pathways that change at an early stage of carcinogenesis provides potentially useful information for early diagnosis and for prevention strategies for human tongue squamous cell carcinomas.
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Xiao-Han
authors.initials: XH
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Urvalek
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Kwame
authors.initials: K
authors.lastname: Osei-Sarfo
authors.affiliation: Genomics Resources Core Facility, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Tuo
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Scognamiglio
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Lorraine J
authors.initials: LJ
authors.lastname: Gudas
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000737:chemistry; D000818:Animals; D014408:Biomarkers, Tumor; D063646:Carcinogenesis / Q000235:genetics*; D002273:Carcinogens / Q000737:chemistry; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002453:Cell Cycle; D030541:Databases, Genetic; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009062:Mouth Neoplasms / Q000378:metabolism*; D015363:Quinolones / Q000737:chemistry; D017423:Sequence Analysis, RNA; D014062:Tongue Neoplasms / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C120195:4-nitroquinolone-1-oxide; D014408:Biomarkers, Tumor; D002273:Carcinogens; D015363:Quinolones; D015112:4-Nitroquinoline-1-oxide
keywords: RNA-seq; cancer diagnosis; squamous cell carcinoma; tongue lesions