A Novel Molecular Signature Identified by Systems Genetics Approach Predicts Prognosis in Oral Squamous Cell Carcinoma

• DOI: 10.1371/journal.pone.0023452
• Publication Date: 2011-08-11T23:05:26Z
• Authors: Chien-Hua Peng; Chun-Ta Liao; Shih-Chi Peng; Yin-Ju Chen; Ann-Joy Cheng; Jyh-Lyh Juang; Chi-Ying Tsai; Tse-Ching Chen; Yung-Jen Chuang; Chuan-Yi Tang; Wen-Ping Hsieh; Tzu-Chen Yen
• Keywords: 0301 basic medicine; DNA Copy Number Variations; Transcription, Genetic; Science; Proto-Oncogene Proteins c-myc; 03 medical and health sciences; Quantitative Trait, Heritable; Humans; Gene Regulatory Networks; Proportional Hazards Models; Genome, Human; Gene Expression Profiling; Systems Biology; Q; R; Prognosis; 3. Good health; Gene Expression Regulation, Neoplastic; Survival Rate; Genetic Loci; Carcinoma, Squamous Cell; Medicine; Mouth Neoplasms; Research Article; Chromosomes, Human, Pair 8; Genes, Neoplasm

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.