title: A novel molecular signature identified by systems genetics approach predicts prognosis in oral squamous cell carcinoma.
abstract: Molecular methods for predicting prognosis in patients with oral cavity squamous cell carcinoma (OSCC) are urgently needed, considering its high recurrence rate and tendency for metastasis. The present study investigated the genetic basis of variations in gene expression associated with poor prognosis in OSCC using Affymetrix SNP 6.0 and Affymetrix GeneChip Human Gene 1.0 ST arrays. We identified recurrent DNA amplifications scattered from 8q22.2 to 8q24.3 in 112 OSCC specimens. These amplicons demonstrated significant associations with increased incidence of extracapsular spread, development of second primary malignancies, and poor survival. Fluorescence in situ hybridization, in a validation panel consisting of 295 cases, confirmed these associations. Assessment of the effects of copy number variations (CNVs) on genome-wide variations in gene expression identified a total of 85 CNV-associated transcripts enriched in the MYC-centered regulatory network. Twenty-four transcripts associated with increased risk of second primary malignancies, tumor relapse, and poor survival. Besides MYC itself, a novel dysregulated MYC module plays a key role in OSCC carcinogenesis. This study identified a candidate molecular signature associated with poor prognosis in OSCC patients, which may ultimately facilitate patient-tailored selection of therapeutic strategies.
authors.affiliation: Resource Center for Clinical Research, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Chien-Hua
authors.initials: CH
authors.lastname: Peng
authors.forename: Chun-Ta
authors.initials: CT
authors.lastname: Liao
authors.forename: Shih-Chi
authors.initials: SC
authors.lastname: Peng
authors.forename: Yin-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Ann-Joy
authors.initials: AJ
authors.lastname: Cheng
authors.forename: Jyh-Lyh
authors.initials: JL
authors.lastname: Juang
authors.forename: Chi-Ying
authors.initials: CY
authors.lastname: Tsai
authors.forename: Tse-Ching
authors.initials: TC
authors.lastname: Chen
authors.forename: Yung-Jen
authors.initials: YJ
authors.lastname: Chuang
authors.forename: Chuan-Yi
authors.initials: CY
authors.lastname: Tang
authors.forename: Wen-Ping
authors.initials: WP
authors.lastname: Hsieh
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D019655:Quantitative Trait, Heritable; D015996:Survival Rate; D049490:Systems Biology; D014158:Transcription, Genetic
chemical_list: D016271:Proto-Oncogene Proteins c-myc