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Gene Expression Profiles of Head and Neck Carcinomas from Sudanese and Norwegian Patients Reveal Common Biological Pathways Regardless of Race and Lifestyle

Authors' Affiliations: Departments of ¹ Informatics and ² Oral Sciences-Periodontology; ³ Center for Medical Genetics and Molecular Medicine; ⁴ Department of Biomedicine, Section of Biochemistry and Molecular Biology; ⁵ Department of Surgical Sciences, Section of Otorhinolaryngology; and ⁶ Department of Oral Sciences-Oral Pathology and Forensic Odontology, Haukeland University Hospital; ⁷ Computational Biology Unit, Bergen Centre for Computational Science, University of Bergen, Bergen, Norway; and ⁸ Department of Oral and Maxillofacial Surgery, Khartoum Dental Teaching Hospital, Sudan

Requests for reprints: Salah O. Ibrahim, Department of Biomedicine, Section of Biochemistry and Molecular Biology, University of Bergen, Jonas Lies Vei 91, 5009 Bergen, Norway. Phone: 47-55-586-423; Fax: 47-55-586-360; E-mail: sosman{at}biomed.uib.no.

Purpose: To explore possible range of gene expression profiles in head and neck squamous cell carcinomas (HNSCC) and pairwised normal controls from Sudanese (n = 72) and Norwegian (n = 45) patients using a 15K cDNA microarray and to correlate the findings with clinicopathologic variables.

Experimental Design: Samples from Sudan were grouped according to anatomic location/patients' habit of toombak (snuff) use, and 37 pools of 2 to 11 tumors matched to 37 pools of their normal controls from the same patients, respectively, were prepared. For Norway, eight pools of 3 to 11 tumors matched to eight pools of their normal controls from the same patients, respectively, were prepared according to anatomic location. Pools (n = 45) were hybridized to microarrays. For controls, 33 of the pools were hybridized against Human Reference RNA. Scanned array images were recorded, and data analysis was done in groups. For verification, results for selected genes were analyzed using quantitative real-time PCR/immunohistochemistry.

Results: We identified 136 genes from Sudan and 154 from Norway as differentially expressed between tumors and controls. Changes of the genes found were confirmed in >70% of the pools by hybridization against Reference RNA. Seventy-three genes and three main pathways (signal transduction, cell communication, and ligand-receptor interaction) were of relevance to the HNSCCs from both countries. Hierarchical clustering of the 73 genes identified subclasses of mixed tumors from the two populations, two independent subgroups for Norwegian tumors by their anatomic sites, and five subgroups for Sudanese tumors by their toombak habits. Quantitative real-time PCR/immunohistochemistry validated the microarray-based data.

Conclusions: Differences in gene expression between tumor and nontumor tissues were identified in HNSCCs. Analysis of the two population groups revealed a common set of 73 genes within three main biological pathways. This indicates that the development of HNSCCs is mediated by similar biological pathways regardless of differences related to race, ethnicity, lifestyle, and/or exposure to environmental carcinogens. Of particular interest, however, was the valuable association of gene expression signature found with toombak use and anatomic site of the tumors.