title: Gene expression profiling reveals biological pathways responsible for phenotypic heterogeneity between UK and Sri Lankan oral squamous cell carcinomas.
abstract: OBJECTIVE
  It is well recognized that oral squamous cell carcinoma (OSCC) cases from Asia that are associated with betel quid chewing are phenotypically distinct to those from Western countries that are predominantly caused by smoking/drinking, but the molecular basis of these differences are largely unknown. The aim of this study is to examine gene expression, related carcinogenic pathways and molecular processes that might be responsible for the phenotypic heterogeneity of OSCC between UK and Sri Lankan population groups.
  
  
  METHODS
  We have compared the gene expression profiles of OSCCs and normal oral mucosal tissues from both Sri Lankan and UK individuals using Affymetrix gene expression arrays. The generated data was interrogated using significance analysis of microarrays and Ingenuity Pathway Analysis (IPA).
  
  
  RESULTS
  The gene expression profiles of UK and Sri Lankan OSCC are similar in many respects to other oral cancer expression profiles reported in the literature and were mainly similar to each other. However, genes involved in tumor invasion, metastasis and recurrence were more obviously associated with UK tumors as opposed to those from Sri Lanka.
  
  
  CONCLUSIONS
  The development of OSCCs in both UK and Sri Lankan populations appears largely mediated by similar biological pathways despite the differences related to race, ethnicity, lifestyle, and/or exposure to environmental carcinogens. However, IPA revealed a highly activated "Cell-mediated Immune Response" in Sri Lankan normal and tumor samples relative to UK cohorts. It seems likely, therefore, that any future attempts to personalize treatment for OSCC patients will need to be different in Western and Asian countries to reflect differences in gene expression and the immune status of the patients.
authors.affiliation: Department of Oral Surgery, Edinburgh Postgraduate Dental Institute, University of Edinburgh, Lauriston Place, Lauriston Building, EH3 9HA Edinburgh, UK. Electronic address: anas.saeed@ed.ac.uk.
authors.forename: Anas A
authors.initials: AA
authors.lastname: Saeed
authors.affiliation: Applied Bioinformatics of Cancer, University of Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, UK. Electronic address: andrew.sims@ed.ac.uk.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Sims
authors.affiliation: Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and the London School of Dentistry, Queen Mary University of London, Turner Street, Whitechapel E1 2AD, UK. Electronic address: stephensprime@gmail.com.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Prime
authors.affiliation: Dental Research and Training Unit, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: ipaterson@um.edu.my.
authors.forename: Ian
authors.initials: I
authors.lastname: Paterson
authors.affiliation: School of Cancer Sciences, Birmingham Cancer Research UK Centre, Birmingham University, Edgbaston B15 2TT, Birmingham, UK. Electronic address: p.g.murray@bham.ac.uk.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Murray
authors.affiliation: Head and Neck Directorate NHS Lothian and University of Edinburgh, UK. Electronic address: vlopes@staffmail.ed.ac.uk.
authors.forename: Victor R
authors.initials: VR
authors.lastname: Lopes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000453:epidemiology; D001114:Areca; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008409:Mastication; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000208:ethnology / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D013188:Sri Lanka / Q000208:ethnology; D006113:United Kingdom / Q000208:ethnology
keywords: Biological pathways; Gene expression profiling; Microarray; Oral squamous cell carcinoma; Sri Lanka; UK