Gene expression profiling in head and neck squamous cell carcinoma: Clinical perspectives

Institut National de la Santé et de la Recherche Médicale, U661 Montpellier F-34094, France
Head & Neck (Impact Factor: 2.64). 12/2010; 32(12):1712 - 1719. DOI: 10.1002/hed.21491


Background.To date, more than 60 gene expression profiling (GEP) studies have been published in the field of head and neck squamous cell carcinoma (HNSCC) with variable objectives, methods, and results.Methods.The purpose of this study was to present a state-of-the-art review of GEP in HNSCC focusing on the current advances and perspectives for clinical applications.Results.Gene expression signatures have been developed to identify screening and diagnostic molecular markers, to improve tumor staging (cervical lymph node and distant metastasis prediction), to differentiate lung metastasis of HNSCC from primary lung squamous cell carcinoma, to predict tumor response to chemoradiotherapy, and to provide outcome predictors.Conclusion.Some transcriptional signatures that could improve HNSCC management have been identified, but further analyses are required to properly validate and to precisely evaluate their clinical relevance. After an exploratory phase, the completion of large scale projects with stringent methodology is now necessary to transfer GEP from bench to bedside. © 2010 Wiley Periodicals, Inc. Head Neck, 2010

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    • "The genetic alterations that drive the development and progression of OSCC are starting to be elucidated, but the disease is characterized by significant clinical and genetic heterogeneity [10]. A considerable number of gene expression microarray studies investigating OSCC in Western populations have been published (60 studies reviewed here) [11], though relatively few studies have reported OSCC cases from Asian countries [12] [13] [14] [15], which could be attributed to the cost of the technology or access to suitable clinical material. "
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    ABSTRACT: 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. 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). 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. 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. Copyright © 2014. Published by Elsevier Ltd.
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    • "To date, more than 60 gene expression profiling studies have been published in the field of head and neck squamous cell carcinoma (SCCHN) with variable objectives , methods and results [3]. We have shown that gene expression profiles can relate to sensitivity to cisplatin in SCCHN cell lines [4]. "
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    ABSTRACT: Global gene expression analysis was performed on pre-treatment biopsies from patients with squamous cell carcinoma of the head and neck (SCCHN) to discover biomarkers that can predict outcome of radiation based therapy. We initially evaluated RNA expression using cDNA microarray analysis of 38 patients that received radiotherapy (RT). The five strongest candidates (VEGF, BCL-2, CLAUDIN-4, YAP-1 and c-MET) were then analysed in pre-treatment biopsies in a second group of 86 patients who received radiation based treatment using immunohistochemical staining (IHC), prepared by tissue microarray. In the first population, 13 of 38 (34%) had no (NR) or partial response (PR) to RT. cDNA microarrays revealed 60 genes that were linked to response to therapy. In the second series, 12 of 86 patients (14%) experienced NR or PR to CRT. Cause specific survival (CSS) and recurrence free survival (RFS) at 2 years was 85% and 90% and at 3 years 81% and 84%, respectively. Biomarkers predictive for NR/PR were increased expression of vascular endothelial growth factor (VEGF) (p=0.02), Yes-associated protein (YAP-1) (p<0.01), CLAUDIN-4 (p<0.01), c-MET (p<0.01) and BCL-2 (p=0.02). Biomarkers predictive of poor RFS were YAP-1 (p=0.01) and BCL-2 (p<0.01). Biomarkers predictive of poor CSS were YAP-1 (p=0.04), VEGF (p=0.03) and CLAUDIN-4 (p=0.03). Furthermore, when YAP-1 and c-MET expression levels were combined the prediction of radio-resistance was increased. All five biomarkers were predictive of poor response to radiation based therapy. In particular, YAP-1 and c-MET have synergistic power and could be used to make treatment decisions.
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