Gene expression profiling to predict outcome after chemoradiation in head and neck cancer.
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.
Pramana
Jimmy
J
Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Van den Brekel
Michiel W M
MW
van Velthuysen
Marie-Louise F
ML
Wessels
Lodewijk F A
LF
Nuyten
Dimitry S
DS
Hofland
Ingrid
I
Atsma
Douwe
D
Pimentel
Nuno
N
Hoebers
Frank J P
FJ
Rasch
Coen R N
CR
Begg
Adrian C
AC
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
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin