Molecular Classification of Head and Neck Tumors Using cDNA Microarray Analysis to Detect Prognosis and Response to Therapy
Previous research by our group using genetic microarray analysis of HNSCC and normal
keratinocytes has identified two distinct groups of genetic expression based on clustering
patterns of a subgroup of genes. Clinical data was summarized for each group and overall,
patient segregation by gene expression profiling was a better predictor of outcome than
clinicopathological variables. Further analysis identified 375 genes that discriminate
between the genotypic subtypes of HNSCC. Overall, our preliminary data has shown that the
pattern of global gene expression in a HNSCC specimen can be used as a predictor of
prognosis. We isolated subsets of genes showing the greatest patterns of divergence in gene
expression. We have also identified 366 over-expressed and 246 underexpressed genes when
comparing primary tumor to normal surgical margins and have identified a similar number of
genes whose expression has changed when comparing primary tumor to lymph node metastasis.
Combining these data sets we have identified genes which consistently increase or decrease
expression during progression from normal tissue to primary tumor, and subsequently to
metastatic node. We have selected several candidate genes for subsequent analysis using
HNSCC tissue arrays. Through DNA microarray analysis, a more detailed knowledge of the
malignant transformation process, and alterations with therapy, in these patients may be
obtained. This study will seek to characterize genetic profiles on 200 patients and
correlate this data with patient's clinical data. Ultimately it is hoped that tumor
specific genetic abnormalities may be identified which could provide targets for treatment
strategies such as gene therapy, immunotherapy, or other interventions.
To evaluate gene expression patterns in human head and neck squamous cell carcinoma and
correlate this with treatment response, both surgical and non-surgical.
To identify a series of diagnostic markers in blood, urine and/or sputum for head and neck
squamous cell carcinoma and study the mechanism of action of these proteins.
Observational Model: Cohort, Time Perspective: Prospective
correlation of treatment response and prognosis (time to recurrence and survival) with genetic expression profile
Richard V Smith
Montefiore Medical Center
United States: Institutional Review Board
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