Research Papers:
Gene expression profiling signatures for the diagnosis and prevention of oral cavity carcinogenesis-genome-wide analysis using RNA-seq technology
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Abstract
Xiao-Han Tang1, Alison M. Urvalek1,*, Kwame Osei-Sarfo1,*, Tuo Zhang2, Theresa Scognamiglio3 and Lorraine J. Gudas1
1 Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA
2 Genomics Resources Core Facility, Weill Cornell Medical College, New York, NY, USA
3 Department of Pathology, Weill Cornell Medical College, New York, NY, USA
* These authors have contributed equally to this work
Correspondence to:
Lorraine J. Gudas, email:
Keywords: cancer diagnosis, squamous cell carcinoma, tongue lesions, RNA-seq
Received: February 10, 2015 Accepted: May 31, 2015 Published: June 10, 2015
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.
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