Genes involved in radiation therapy response in head and neck cancers.
OBJECTIVE
This is a pilot study designed to identify gene expression profiles able to stratify head and neck squamous cell carcinoma (HNSCC) tumors that may or may not respond to chemoradiation or radiation therapy.


METHODS
We prospectively evaluated 14 HNSCC specimens, arising from patients undergoing chemoradiotherapy or radiotherapy alone with curative intent. A complete response was assessed by clinical evaluation with no evidence of gross tumor after a 2-year follow-up period.


METHODS
Residual biopsy samples from eight complete responders (CR) and six nonresponders (NR) were evaluated by genome-wide gene expression profiling using HG-U133A 2.0 arrays. Univariate parametric t-tests with proportion of false discoveries controlled by multivariate permutation tests were used to identify genes with significantly different gene expression levels between CR and NR cases. Six different prediction algorithms were used to build gene predictor lists. Three representative genes showing 100% crossvalidation support after leave-one-out crossvalidation (LOOCV) were further validated using real-time QRT-PCR.


RESULTS
We identified 167 significant probe sets that discriminate between the two classes, which were used to build gene predictor lists. Thus, 142 probe sets showed an accuracy of prediction ranging from 93% to 100% across all six prediction algorithms. The genes represented by these 142 probe sets were further classified into different functional networks that included cellular development, cellular movement, and cancer.


CONCLUSIONS
The results presented herein offer encouraging preliminary data that may provide a basis for a more precise prognosis of HNSCC, as well as a molecular-based therapy decision for the management of these cancers.
Dumur
Catherine I
CI
Department of Pathology, Virginia Commonwealth University, Richmond, Virginia 23298, USA. cdumur@mcvh-vcu.edu
Ladd
Amy C
AC
Wright
Harry V
HV
Penberthy
Lynne T
LT
Wilkinson
David S
DS
Powers
Celeste N
CN
Garrett
Carleton T
CT
DiNardo
Laurence J
LJ
D000328:Adult; D000368:Aged; D000465:Algorithms; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction