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Status |
Public on Feb 02, 2014 |
Title |
Gene expression profiling reveals biological pathways responsible for phenotypic heterogeneity between UK and Sri Lankan OSCC |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Background: Oral squamous cell carcinoma (OSCC) is a major world health problem with over 400,000 new cases diagnosed annually. Despite advances in surgery and chemo-radiotherapy, the 5 year survival has remained roughly constant at approximately 50% for several decades. The disease is characterized by both clinical and genetic heterogeneity, so elucidating the molecular basis of this heterogeneity would have significant clinical implications. It is well recognized that OSCCs from Asia that are associated with betel quid chewing are phenotypically distinct from those from the West that are predominantly caused by smoking/drinking, but the genetic basis of these differences are largely unknown. The aim of this study is to examine the most related genetic factors, carcinogenic related 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. 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. Interestingly, Ingenuity Pathway Analysis (IPA) revealed a highly activated cell-mediated immune response in both Sri Lankan normal and tumor samples relative to UK cohorts, which may, in part, explain the less aggressive behavior of these betel quid-induced OSCCs. Conclusion: 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.
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Overall design |
All biopsy specimens of OSCC and normal oral mucosa were harvested with appropriate ethical approval and informed consent of individual patients (LREC 0769). Identical protocols for tissue collection and processing were used in both countries. OSCC samples were obtained from sequential incident cases treated by a single consultant surgeon from 2001 to 2004 at University Hospital of Birmingham, NHS Foundation Trust, Birmingham, UK, and Kandy General Hospital, Kandy, Sri Lanka. A total of 21 UK and 27 Sri Lankan samples yielded RNA of sufficient quality and quantity for microarray analysis. In addition, 8 normal oral mucosa specimens (five samples from UK & three samples from Sri Lankan population) were also profiled. All normal samples were from non-smokers, who did not chew betel quid and did not consume in excess of the national recommended weekly gender allowance of alcohol. Normal samples were taken from individuals with no history of cancer and had no first degree relatives with a history of cancer.
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Contributor(s) |
Saeed AA, Sims AH, Prime SS, Paterson I, Murray PG, Lopes VR |
Citation(s) |
25560800 |
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Submission date |
Sep 19, 2013 |
Last update date |
Mar 25, 2019 |
Contact name |
anas amjad saeed |
E-mail(s) |
anas.nhsuk@yahoo.com
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Phone |
00447503572732
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Organization name |
edinburgh dental institute
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Department |
oral surgery
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Street address |
Lauriston building
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City |
edinburgh |
ZIP/Postal code |
eh3 9 ha |
Country |
United Kingdom |
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Platforms (2) |
GPL201 |
[HG-Focus] Affymetrix Human HG-Focus Target Array |
GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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Samples (56)
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GSM1234782 |
Normal OSC tissue from UK samples, M4 |
GSM1234783 |
Normal OSC tissue from UK samples, V5 |
GSM1234784 |
Normal OSC tissue from Sri Lankan samples, KN2 |
GSM1234785 |
Normal OSC tissue from Sri Lankan samples, KN3 |
GSM1234786 |
Normal OSC tissue from Sri Lankan samples, KN5 |
GSM1234787 |
OSCC from UK patients, OCS 001 |
GSM1234788 |
OSCC from UK patients, OCS 003 |
GSM1234789 |
OSCC from UK patients, OCS 004 |
GSM1234790 |
OSCC from UK patients, OCS 006 |
GSM1234791 |
OSCC from UK patients, OCS 007 |
GSM1234792 |
OSCC from UK patients, OCS 008 |
GSM1234793 |
OSCC from UK patients, OCS 011 |
GSM1234794 |
OSCC from UK patients, OCS 012 |
GSM1234795 |
OSCC from UK patients, OCS 013 |
GSM1234796 |
OSCC from UK patients, OCS 014 |
GSM1234797 |
OSCC from UK patients, OCS 015 |
GSM1234798 |
OSCC from UK patients, OCS 016 |
GSM1234799 |
OSCC from UK patients, OCS 020 |
GSM1234800 |
OSCC from UK patients, OCS 022 |
GSM1234801 |
OSCC from UK patients, OCS 024 |
GSM1234802 |
OSCC from UK patients, OCS 025 |
GSM1234803 |
OSCC from UK patients, OCS 026 |
GSM1234804 |
OSCC from UK patients, OCS 027 |
GSM1234805 |
OSCC from UK patients, OCS 029 |
GSM1234806 |
OSCC from UK patients, OCS 031 |
GSM1234807 |
OSCC from UK patients, OCS 032 |
GSM1234808 |
OSCC from Sri Lankan patients, KC01 |
GSM1234809 |
OSCC from Sri Lankan patients, KC02 |
GSM1234810 |
OSCC from Sri Lankan patients, KC04 |
GSM1234811 |
OSCC from Sri Lankan patients, KC07 |
GSM1234812 |
OSCC from Sri Lankan patients, KC09 |
GSM1234813 |
OSCC from Sri Lankan patients, KC013 |
GSM1234814 |
OSCC from Sri Lankan patients, KC015 |
GSM1234815 |
OSCC from Sri Lankan patients, KC016 |
GSM1234816 |
OSCC from Sri Lankan patients, KC017 |
GSM1234817 |
OSCC from Sri Lankan patients, KC019 |
GSM1234818 |
OSCC from Sri Lankan patients, KC20 |
GSM1234819 |
OSCC from Sri Lankan patients, KC21 |
GSM1234820 |
OSCC from Sri Lankan patients, KC24 |
GSM1234821 |
OSCC from Sri Lankan patients, KC25 |
GSM1234822 |
OSCC from Sri Lankan patients, KC26 |
GSM1234823 |
OSCC from Sri Lankan patients, KC29 |
GSM1234824 |
OSCC from Sri Lankan patients, KC31 |
GSM1234825 |
OSCC from Sri Lankan patients, KC32 |
GSM1234826 |
OSCC from Sri Lankan patients, KC38 |
GSM1234827 |
OSCC from Sri Lankan patients, KC39 |
GSM1234828 |
OSCC from Sri Lankan patients, KC41 |
GSM1234829 |
OSCC from Sri Lankan patients, KC44 |
GSM1234830 |
OSCC from Sri Lankan patients, KC45 |
GSM1234831 |
OSCC from Sri Lankan patients, KC46 |
GSM1234832 |
OSCC from Sri Lankan patients, KC47 |
GSM1234833 |
OSCC from Sri Lankan patients, KC51 |
GSM1234834 |
OSCC from Sri Lankan patients, KC53 |
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Relations |
BioProject |
PRJNA219517 |
Supplementary file |
Size |
Download |
File type/resource |
GSE51010_RAW.tar |
106.7 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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