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基因表达谱分析揭示了英国和斯里兰卡口腔鳞状细胞癌之间表型异质性所涉及的生物学途径。

Gene expression profiling reveals biological pathways responsible for phenotypic heterogeneity between UK and Sri Lankan oral squamous cell carcinomas.

作者信息

Saeed Anas A, Sims Andrew H, Prime Stephen S, Paterson Ian, Murray Paul G, Lopes Victor R

机构信息

Department of Oral Surgery, Edinburgh Postgraduate Dental Institute, University of Edinburgh, Lauriston Place, Lauriston Building, EH3 9HA Edinburgh, UK.

Applied Bioinformatics of Cancer, University of Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, UK.

出版信息

Oral Oncol. 2015 Mar;51(3):237-46. doi: 10.1016/j.oraloncology.2014.12.004. Epub 2015 Jan 2.

DOI:10.1016/j.oraloncology.2014.12.004
PMID:25560800
Abstract

OBJECTIVES

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.

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.

摘要

目的

众所周知,亚洲与嚼槟榔相关的口腔鳞状细胞癌(OSCC)病例在表型上与西方国家主要由吸烟/饮酒引起的病例不同,但这些差异的分子基础很大程度上尚不清楚。本研究的目的是研究可能导致英国和斯里兰卡人群中OSCC表型异质性的基因表达、相关致癌途径和分子过程。

方法

我们使用Affymetrix基因表达阵列比较了斯里兰卡和英国个体的OSCC及正常口腔黏膜组织的基因表达谱。使用微阵列显著性分析和 Ingenuity 通路分析(IPA)对生成的数据进行分析。

结果

英国和斯里兰卡OSCC的基因表达谱在许多方面与文献中报道的其他口腔癌表达谱相似,且彼此之间主要相似。然而,与肿瘤侵袭、转移和复发相关的基因在英国肿瘤中比在斯里兰卡肿瘤中更明显。

结论

尽管英国和斯里兰卡人群在种族、民族、生活方式和/或接触环境致癌物方面存在差异,但两国OSCC的发生似乎在很大程度上由相似的生物学途径介导。然而,IPA显示,相对于英国队列,斯里兰卡正常和肿瘤样本中的“细胞介导的免疫反应”高度激活。因此,未来任何针对OSCC患者进行个性化治疗的尝试在西方国家和亚洲国家可能需要有所不同,以反映患者基因表达和免疫状态的差异。

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