title: Gene expression profiling to predict outcome after chemoradiation in head and neck cancer.
abstract: OBJECTIVE
  The goal of the present study was to improve prediction of outcome after chemoradiation in advanced head and neck cancer using gene expression analysis.
  
  
  METHODS
  We collected 92 biopsies from untreated head and neck cancer patients subsequently given cisplatin-based chemoradiation (RADPLAT) for advanced squamous cell carcinomas (HNSCC). After RNA extraction and labeling, we performed dye swap experiments using 35k oligo-microarrays. Supervised analyses were performed to create classifiers to predict locoregional control and disease recurrence. Published gene sets with prognostic value in other studies were also tested.
  
  
  RESULTS
  Using supervised classification on the whole series, gene sets separating good and poor outcome could be found for all end points. However, when splitting tumors into training and validation groups, no robust classifiers could be found. Using Gene Set Enrichment analysis, several gene sets were found to be enriched in locoregional recurrences, although with high false-discovery rates. Previously published signatures for radiosensitivity, hypoxia, proliferation, "wound," stem cells, and chromosomal instability were not significantly correlated with outcome. However, a recently published signature for HNSCC defining a "high-risk" group was shown to be predictive for locoregional control in our dataset.
  
  
  CONCLUSIONS
  Gene sets can be found with predictive potential for locoregional control after combined radiation and chemotherapy in HNSCC. How treatment-specific these gene sets are needs further study.
authors.affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Pramana
authors.forename: Michiel W M
authors.initials: MW
authors.lastname: Van den Brekel
authors.forename: Marie-Louise F
authors.initials: ML
authors.lastname: van Velthuysen
authors.forename: Lodewijk F A
authors.initials: LF
authors.lastname: Wessels
authors.forename: Dimitry S
authors.initials: DS
authors.lastname: Nuyten
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hofland
authors.forename: Douwe
authors.initials: D
authors.lastname: Atsma
authors.forename: Nuno
authors.initials: N
authors.lastname: Pimentel
authors.forename: Frank J P
authors.initials: FJ
authors.lastname: Hoebers
authors.forename: Coen R N
authors.initials: CR
authors.lastname: Rasch
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Begg
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D010610:Pharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin