Integrative analysis of DNA copy number and gene expression in metastatic oral squamous cell carcinoma identifies genes associated with poor survival

Molecular Cancer

Research

Tessa C Rue¹  Chang Xu²  Neal D Futran²  Eduardo Méndez³  Chu Chen⁴  Melissa P Upton⁵  Yan Liu⁶  Wenhong Fan⁶  Lue Ping Zhao⁷  Pei Wang⁸  David R Doody⁹  John R Houck⁹  Pawadee Lohavanichbutr⁹  Stephen M Schwartz^1,10 

[1] Department of Biostatistics, University of Washington, 98195, Seattle, WA, USA;Department of Otolaryngology-Head and Neck Surgery, University of Washington, 98195, Seattle, WA, USA;Department of Otolaryngology-Head and Neck Surgery, University of Washington, 98195, Seattle, WA, USA;Program in Epidemiology, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 98109, Seattle, WA, USA;Clinical Research Division, Fred Hutchinson Cancer Research Center, 98109, Seattle, WA, USA;Surgery and Perioperative Care Service, VA Puget Sound Health Care System, 98108, Seattle, Washington, USA;Department of Otolaryngology-Head and Neck Surgery, University of Washington, 98195, Seattle, WA, USA;Program in Epidemiology, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 98109, Seattle, WA, USA;Department of Epidemiology, University of Washington, 98195, Seattle, WA, USA;Department of Pathology, University of Washington, 98195, Seattle, WA, USA;Program in Biostatistics & Biomathematics, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 98109, Seattle, WA, USA;Program in Biostatistics & Biomathematics, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 98109, Seattle, WA, USA;Department of Biostatistics, University of Washington, 98195, Seattle, WA, USA;Program in Cancer Prevention and Biostatistics, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 98109, Seattle, WA, USA;Program in Epidemiology, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 98109, Seattle, WA, USA;Program in Epidemiology, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 98109, Seattle, WA, USA;Department of Epidemiology, University of Washington, 98195, Seattle, WA, USA;

关键词: Oral Squamous Cell Carcinoma;    Oral Squamous Cell Carcinoma;    Oral Squamous Cell Carcinoma Cell;    Oral Squamous Cell Carcinoma Patient;    Copy Number Aberration;   

DOI  :  10.1186/1476-4598-9-143

 received in 2010-02-10, accepted in 2010-06-11,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundLymphotropism in oral squamous cell carcinoma (OSCC) is one of the most important prognostic factors of 5-year survival. In an effort to identify genes that may be responsible for the initiation of OSCC lymphotropism, we examined DNA copy number gains and losses and corresponding gene expression changes from tumor cells in metastatic lymph nodes of patients with OSCC.ResultsWe performed integrative analysis of DNA copy number alterations (CNA) and corresponding mRNA expression from OSCC cells isolated from metastatic lymph nodes of 20 patients using Affymetrix 250 K Nsp I SNP and U133 Plus 2.0 arrays, respectively. Overall, genome CNA accounted for expression changes in 31% of the transcripts studied. Genome region 11q13.2-11q13.3 shows the highest correlation between DNA CNA and expression. With a false discovery rate < 1%, 530 transcripts (461 genes) demonstrated a correlation between CNA and expression. Among these, we found two subsets that were significantly associated with OSCC (n = 122) when compared to controls, and with survival (n = 27), as tested using an independent dataset with genome-wide expression profiles for 148 primary OSCC and 45 normal oral mucosa. We fit Cox models to calculate a principal component analysis-derived risk-score for these two gene sets ('122-' or '27-transcript PC'). The models combining the 122- or 27-transcript PC with stage outperformed the model using stage alone in terms of the Area Under the Curve (AUC = 0.82 or 0.86 vs. 0.72, with p = 0.044 or 0.011, respectively).ConclusionsGenes exhibiting CNA-correlated expression may have biological impact on carcinogenesis and cancer progression in OSCC. Determination of copy number-associated transcripts associated with clinical outcomes in tumor cells with an aggressive phenotype (i.e., cells metastasized to the lymph nodes) can help prioritize candidate transcripts from high-throughput data for further studies.

【 授权许可】

Unknown   
© Xu et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.