Volume 42, Issue 2 pp. 312-320
ORIGINAL ARTICLE

Alterations in genetic pathways following radiotherapy for head and neck cancer

Arash O. Naghavi MD, MS

Arash O. Naghavi MD, MS

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida

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Youngchul Kim PhD

Youngchul Kim PhD

Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida

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George Q. Yang MD

George Q. Yang MD

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida

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Kamran A. Ahmed MD

Kamran A. Ahmed MD

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida

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Jimmy J. Caudell MD, PhD

Corresponding Author

Jimmy J. Caudell MD, PhD

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida

Correspondence

Jimmy J. Caudell, 12902 Magnolia Drive, Tampa, FL 33612.

Email: [email protected]

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First published: 13 December 2019
Citations: 4
Section Editor: James Rocco

Abstract

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.

CONFLICT OF INTEREST

The authors declare no potential conflicts of interests.

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