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

Radiation Oncology Journal 2020년 38권 2호 p.99 ~ 108
김수일, 강정욱, 노주경, 정해림, 이정우, 공문규, 은영규,
소속 상세정보
김수일 ( Kim Su-Il ) - Kyung Hee University Graduate School Department of Biomedical Science and Technology
강정욱 ( Kang Jeong-Wook ) - Kyung Hee University Medical Center Department of Otolaryngology-Head and Neck Surgery
노주경 ( Noh Joo-Kyung ) - Kyung Hee University Graduate School Department of Biomedical Science and Technology
정해림 ( Jung Hae-Rim ) - Kyung Hee University Medical Center Department of Otolaryngology-Head and Neck Surgery
이정우 ( Lee Jung-Woo ) - Kyung Hee University School of Dentistry Department of Oral and Maxillofacial Surgery
공문규 ( Kong Moon-Kyoo ) - Kyung Hee University Medical Center Department of Radiation Oncology
은영규 ( Eun Young-Gyu ) - Kyung Hee University Medical Center Department of Otolaryngology-Head and Neck Surgery

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.

키워드

Head and neck cancer; Radiation; Prediction; Treatment

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