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Oral Oncol. 2014 Mar;50(3):200-7. doi: 10.1016/j.oraloncology.2013.12.009. Epub 2014 Jan 1.

The gene expression profile of inflammatory, hypoxic and metabolic genes predicts the metastatic spread of human head and neck squamous cell carcinoma.

Author information

1
Department of Medical Oncology, Centre Henri Becquerel, IRON, Rouen, France; INSERM U918, Centre Henri Becquerel, IRIB, Rouen, France. Electronic address: fclatot@yahoo.fr.
2
Department of Medical Oncology, Centre Henri Becquerel, IRON, Rouen, France; Department of Medical Oncology, Centre François Baclesse, Caen, France.
3
INSERM U918, Centre Henri Becquerel, IRIB, Rouen, France.
4
Department of Pathology, Centre Henri Becquerel, Rouen, France.
5
Department of Head and Neck Surgery, Hospital Charles Nicolle, Rouen, France.
6
Department of Head and Neck Surgery, Centre Henri Becquerel, Rouen, France.
7
Department of Pathology, Hospital Charles Nicolle, Rouen, France.
8
PRIMACEN, the Cell Imaging Platform of Normandy, IRIB, Faculty of Sciences, University of Rouen, Mont-Saint-Aignan, France.
9
INSERM U918, Centre Henri Becquerel, IRIB, Rouen, France; Department of Pathology, Centre Henri Becquerel, Rouen, France.

Abstract

OBJECTIVES:

To assess the prognostic value of the expression profile of the main genes implicated in hypoxia, glucose and lactate metabolism, inflammation, angiogenesis and extracellular matrix interactions for the metastatic spread of head and neck squamous cell carcinoma.

PATIENTS AND METHODS:

Using a high-throughput qRT-PCR, we performed an unsupervised clustering analysis based on the expression of 42 genes for 61 patients. Usual prognostic factors and clustering analysis results were related to metastasis free survival.

RESULTS:

With a median follow-up of 48months, 19 patients died from a metastatic evolution of their head and neck squamous cell carcinoma and one from a local recurrence. The unsupervised clustering analysis distinguished two groups of genes that were related to metastatic evolution. A capsular rupture (p=0.005) and the "cluster CXCL12 low" (p=0.002) were found to be independent prognostic factors for metastasis free survival. Using a Linear Predictive Score methodology, we established a 9-gene model (VHL, PTGER4, HK1, SLC16A4, DLL4, CXCL12, CXCR4, PTGER3 and CA9) that was capable of classifying the samples into the 2 clusters with 90% accuracy.

CONCLUSION:

In this cohort, our clustering analysis underlined the independent prognostic value of the expression of a panel of genes involved in hypoxia and tumor environment. It allowed us to define a 9-gene model which can be applied routinely to classify newly diagnosed head and neck squamous cell carcinoma. If confirmed by an independent prospective study, this approach may help future clinical management of these aggressive tumors.

KEYWORDS:

CXCL12; CXCR4; Clustering analysis; Head and neck squamous cell carcinoma; Metastasis; Oral cancer; Survival

[Indexed for MEDLINE]

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