Project description: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 M-bM-^@M-^\Cell-mediated Immune ResponseM-bM-^@M-^] 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. 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.

Project description: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.

Project description:The mucosae of the oral cavity are different at the histological level but are all exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the anatomical subsites of OPMLs development with occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs). Multiple samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on FCM-sorted nuclei subpopulations based on DI values. Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites. We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this conclusion should be validated in a prospective clinical study. exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the anatomical subsites of OPMLs development with occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs). Multiple samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on FCM-sorted nuclei subpopulations based on DI values. Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites. We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this conclusion should be validated in a prospective clinical study. We analyzed: 19 samples (4 aneuploid and 15 diploid components) deriving from oral potentially malignant lesions without dysplasia obtained of 16 patients; 14 samples (2 aneuploid and 12 diploid components) deriving from oral potentially malignant lesions with dysplasia obtained from 11 patients (two patients had multiple dysplastic lesions); 2 samples from visually normal mucosa in the near field obtained from two patients with dysplastic lesions. All the aneuploid samples had a purity of at least 90%.

Project description:The mucosae of the oral cavity are different at the histological level but are all exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the anatomical subsites of OPMLs development with occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs). Multiple samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on FCM-sorted nuclei subpopulations based on DI values. Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites. We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this conclusion should be validated in a prospective clinical study. exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the anatomical subsites of OPMLs development with occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs). Multiple samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on FCM-sorted nuclei subpopulations based on DI values. Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites. We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this conclusion should be validated in a prospective clinical study.

Dataset Information

Gene expression profiling of oral squamous cell carcinoma

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