Radiat Oncol J.  2020 Jun;38(2):99-108. 10.3857/roj.2020.00136.

Gene signature for prediction of radiosensitivity in human papillomavirus-negative head and neck squamous cell carcinoma

Affiliations
  • 1Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, Korea
  • 2Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University Medical Center, Seoul, Korea
  • 3Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul, Korea
  • 4Division of Lung & Head and Neck Oncology, Department of Radiation Oncology, Kyung Hee University Medical Center, Seoul, Korea

Abstract

Purpose
The probability of recurrence of cancer after adjuvant or definitive radiotherapy in patients with human papillomavirus-negative (HPV(–)) head and neck squamous cell carcinoma (HNSCC) varies for each patient. This study aimed to identify and validate radiation sensitivity signature (RSS) of patients with HPV(–) HNSCC to predict the recurrence of cancer after radiotherapy.
Materials and Methods
Clonogenic survival assays were performed to assess radiosensitivity in 14 HNSCC cell lines. We identified genes closely correlated with radiosensitivity and validated them in The Cancer Genome Atlas (TCGA) cohort. The validated RSS were analyzed by ingenuity pathway analysis (IPA) to identify canonical pathways, upstream regulators, diseases and functions, and gene networks related to radiosensitive genes in HPV(–) HNSCC.
Results
The survival fraction of 14 HNSCC cell lines after exposure to 2 Gy of radiation ranged from 48% to 72%. Six genes were positively correlated and 35 genes were negatively correlated with radioresistance, respectively. RSS was validated in the HPV(–) TCGA HNSCC cohort (n = 203), and recurrence-free survival (RFS) rate was found to be significantly lower in the radioresistant group than in the radiosensitive group (p = 0.035). Cell death and survival, cell-to-cell signaling, and cellular movement were significantly enriched in RSS, and RSSs were highly correlated with each other.
Conclusion
We derived a HPV(–) HNSCC-specific RSS and validated it in an independent cohort. The outcome of adjuvant or definitive radiotherapy in HPV(–) patients with HNSCC can be predicted by analyzing their RSS, which might help in establishing a personalized therapeutic plan.

Keyword

Head and neck squamous cell carcinoma; Radiation sensitivity signature; Cell line; The Cancer Genome Atlas
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