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Open AccessHighly AccessResearch article

Clinical relevance of nine transcriptional molecular markers for the diagnosis of head and neck squamous cell carcinoma in tissue and saliva rinse

Benjamin Lallemant1,2,3,4 email, Alexandre Evrard2,3,4,5 email, Christophe Combescure6,7 email, Heliette Chapuis8 email, Guillaume Chambon1 email, Caroline Raynal2,3,4,5 email, Christophe Reynaud1 email, Omar Sabra1 email, Dominique Joubert2,3,4 email, Frédéric Hollande2,3,4 email, Jean-Gabriel Lallemant1 email, Serge Lumbroso2,3,4,5 email and Jean-Paul Brouillet2,3,4,5 email

Service d'ORL et Chirurgie Maxillo-faciale, Centre Hospitalier Universitaire de Nîmes, Place du Pr. Robert Debré, 30029 Nîmes Cedex 9, France

Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Montpellier F-34094, France

Institut National de la Santé et de la Recherche Médicale, U661 Montpellier F-34094, France

Université Montpellier 1, Montpellier F-34094, France

Laboratoire de Biochimie, Centre Hospitalier Universitaire de Nîmes, Place du Pr. Robert Debré, 30029 Nîmes Cedex 9, France

Service d'Information Médicale et de Biostatistique, Centre Hospitalier Universitaire de Nîmes, Place du Pr. Robert Debré, 30029 Nîmes Cedex 9, France

CRC - Service d'Epidémiologie Clinique, Hôpitaux Universitaires de Genève, Rue Micheli-du-Crest 24, CH-1211 Genève 14, Suisse

Service d'Anatomie et Cyto-pathologie, Centre Hospitalier Universitaire de Nîmes, Place du Pr. Robert Debré, 30029 Nîmes Cedex 9, France

author email corresponding author email

BMC Cancer 2009, 9:370doi:10.1186/1471-2407-9-370

Published: 18 October 2009

Abstract

Background

Analysis of 23 published transcriptome studies allowed us to identify nine genes displaying frequent alterations in HNSCC (FN1, MMP1, PLAU, SPARC, IL1RN, KRT4, KRT13, MAL, and TGM3). We aimed to independently confirm these dysregulations and to identify potential relationships with clinical data for diagnostic, staging and prognostic purposes either at the tissue level or in saliva rinse.

Methods

For a period of two years, we systematically collected tumor tissue, normal matched mucosa and saliva of patients diagnosed with primary untreated HNSCC. Expression levels of the nine genes of interest were measured by RT-qPCR in tumor and healthy matched mucosa from 46 patients. MMP1 expression level was measured by RT-qPCR in the salivary rinse of 51 HNSCC patients and 18 control cases.

Results

Dysregulation of the nine genes was confirmed by the Wilcoxon test. IL1RN, MAL and MMP1 were the most efficient diagnostic markers of HNSCC, with ROC AUC > 0.95 and both sensitivity and specificity above 91%. No clinically relevant correlation was found between gene expression level in tumor and T stage, N stage, tumor grade, global survival or disease-free survival. Our preliminary results suggests that with 100% specificity, MMP1 detection in saliva rinse is potentially useful for non invasive diagnosis of HNSCC of the oral cavity or oropharynx, but technical improvement is needed since sensitivity was only 20%.

Conclusion

IL1RN, MAL and MMP1 are prospective tumor diagnostic markers for HNSCC. MMP1 overexpression is the most promising marker, and its detection could help identify tumor cells in tissue or saliva.


© 1999-2009 BioMed Central Ltd unless otherwise stated. Part of Springer Science+Business Media.