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Alterations in genetic pathways following radiotherapy for head and neck cancer
Arash O Naghavi1, Youngchul Kim2, George Q Yang1
1Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
Background:
Radiotherapy (RT) is an integral component in the treatment of head and neck cancer (HNC).We hypothesized there would be alterations in gene-expression and pathway activity in HNC samples obtained in recurrent HNC that were previously treated with RT, when compared to RT-naïve disease.
Methods:
Patient data was abstracted from a prospectively maintained database. Linear-microarray analysis and supervised gene-set enrichment-analysis were employed to compare RT-naive and recurrent disease after prior-RT.
Results:
A total of 157 patients were analyzed, 96 (61%) were RT-naive and 61 (39%) had RT.After radiation, there was upregulation of genes associated with angiogenesis, protein-translation-machinery, cell-cycle regulation, and growth factors, and downregulation associated with Myc activity, and hypoxic response (all P < .001).Previously irradiated HNC was associated with downregulation in 19/42 genes in the Wnt/B-catenin-pathway (P = .045)and 119/199 genes involved in the MYC target pathway (P = .024).
Conclusion:
Patients with recurrences salvaged surgically post-RT had significant alterations in gene-expression and in Wnt/B-catenin and MYC-target pathways. These pathways may represent potential targets to prevent development of resistance to RT.
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