title: The gene expression profile of inflammatory, hypoxic and metabolic genes predicts the metastatic spread of human head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, Centre Henri Becquerel, IRON, Rouen, France; INSERM U918, Centre Henri Becquerel, IRIB, Rouen, France. Electronic address: fclatot@yahoo.fr.
authors.forename: Florian
authors.initials: F
authors.lastname: Clatot
authors.affiliation: Department of Medical Oncology, Centre Henri Becquerel, IRON, Rouen, France; Department of Medical Oncology, Centre François Baclesse, Caen, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gouérant
authors.affiliation: INSERM U918, Centre Henri Becquerel, IRIB, Rouen, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Mareschal
authors.affiliation: Department of Pathology, Centre Henri Becquerel, Rouen, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Cornic
authors.affiliation: Department of Pathology, Centre Henri Becquerel, Rouen, France.
authors.forename: Anca
authors.initials: A
authors.lastname: Berghian
authors.affiliation: Department of Head and Neck Surgery, Hospital Charles Nicolle, Rouen, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Choussy
authors.affiliation: Department of Head and Neck Surgery, Centre Henri Becquerel, Rouen, France.
authors.forename: Faissal
authors.initials: F
authors.lastname: El Ouakif
authors.affiliation: Department of Pathology, Hospital Charles Nicolle, Rouen, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: François
authors.affiliation: PRIMACEN, the Cell Imaging Platform of Normandy, IRIB, Faculty of Sciences, University of Rouen, Mont-Saint-Aignan, France.
authors.forename: Magalie
authors.initials: M
authors.lastname: Bénard
authors.affiliation: INSERM U918, Centre Henri Becquerel, IRIB, Rouen, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruminy
authors.affiliation: INSERM U918, Centre Henri Becquerel, IRIB, Rouen, France; Department of Pathology, Centre Henri Becquerel, Rouen, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Picquenot
authors.affiliation: INSERM U918, Centre Henri Becquerel, IRIB, Rouen, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jardin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000556:secondary; D005109:Extracellular Matrix / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D019344:Lactic Acid / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012313:RNA / Q000235:genetics
chemical_list: D001786:Blood Glucose; D019344:Lactic Acid; D012313:RNA
keywords: CXCL12; CXCR4; Clustering analysis; Head and neck squamous cell carcinoma; Metastasis; Oral cancer; Survival