A novel molecular signature identified by systems genetics approach predicts prognosis in oral squamous cell carcinoma

• Published in: PloS one Vol. 6; no. 8; p. e23452
• Main Authors: Peng, Chien-Hua, Liao, Chun-Ta, Peng, Shih-Chi, Chen, Yin-Ju, Cheng, Ann-Joy, Juang, Jyh-Lyh, Tsai, Chi-Ying, Chen, Tse-Ching, Chuang, Yung-Jen, Tang, Chuan-Yi, Hsieh, Wen-Ping, Yen, Tzu-Chen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.08.2011; Public Library of Science (PLoS)
• Subjects: Biology; Breast cancer; Cancer genetics; Carcinogenesis; Carcinogens; Carcinoma, Squamous Cell - diagnosis; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - mortality; Chromosomes; Chromosomes, Human, Pair 8 - genetics; Clinical outcomes; Copy number; Deoxyribonucleic acid; DNA; DNA Copy Number Variations - genetics; Fluorescence; Fluorescence in situ hybridization; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks - genetics; Genes; Genes, Neoplasm - genetics; Genetic aspects; Genetic diversity; Genetic Loci - genetics; Genetics; Genome, Human - genetics; Genomes; Genomics; Hospitals; Humans; Lymphoma; Mathematics; Medical prognosis; Medical research; Medicine; Metabolism; Metastases; Mouth Neoplasms - diagnosis; Mouth Neoplasms - genetics; Mouth Neoplasms - mortality; Multiple myeloma; Myc protein; Nuclear medicine; Oral cancer; Oral cavity; Oral squamous cell carcinoma; Otolaryngology; Patients; Prognosis; Proportional Hazards Models; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Quantitative Trait, Heritable; Risk factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Squamous cell carcinoma; Stem cells; Studies; Survival; Survival Rate; Systems Biology; Transcription factors; Transcription, Genetic; China; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0023452

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.