Gene expression profiles of head and neck carcinomas from Sudanese and Norwegian patients reveal common biological pathways regardless of race and lifestyle.
OBJECTIVE
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.


METHODS
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.
Department of Informatics, Haukeland University Hospital, Norway.
Bjarte
B
Dysvik
Endre N
EN
Vasstrand
Roger
R
Løvlie
Osman A-Aziz
OA
Elgindi
Kenneth W
KW
Kross
Hans J
HJ
Aarstad
Anne Chr
AC
Johannessen
Inge
I
Jonassen
Salah O
SO
Ibrahim
D000368:Aged; D034961:Antigens, Nuclear / Q000032:analysis / Q000235:genetics; D044383:Black People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002630:Chemotactic Factors / Q000032:analysis / Q000235:genetics; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D005260:Female; D005353:Fibronectins / Q000032:analysis / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis / Q000235:genetics; D000072200:Ku Autoantigen; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009664:Norway; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D009418:S100 Proteins / Q000032:analysis / Q000235:genetics; D013397:Sudan; D044465:White People / Q000235:genetics
D034961:Antigens, Nuclear; D002630:Chemotactic Factors; D004268:DNA-Binding Proteins; D005353:Fibronectins; D012333:RNA, Messenger; D009418:S100 Proteins; C098997:S100A2 protein, human; D007633:Keratins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen