Gene signature for prediction of radiosensitivity in human papillomavirus-negative head and neck squamous cell carcinoma.
Gene signature for prediction of radiosensitivity in human papillomavirus-negative head and neck squamous cell carcinoma.
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DOI：
10.3857/roj.2020.00136
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发表时间：
2020-06
影响因子：
2.3
通讯作者：
Eun YG
中科院分区：
文献类型：
--
作者：
Kim SI;Kang JW;Noh JK;Jung HR;Lee YC;Lee JW;Kong M;Eun YG
人乳头瘤病毒阴性（HPV（-））头颈部鳞状细胞癌（HNSCC）患者在接受辅助性或确定性放疗后癌症复发的概率因人而异。本研究旨在识别和验证HPV（-）HNSCC患者的放射敏感性特征（RSS），以预测放疗后癌症的复发。进行克隆形成存活测定以评估14个HNSCC细胞系中的放射敏感性。我们确定了与放射敏感性密切相关的基因，并在癌症基因组图谱（TCGA）队列中对其进行了验证。通过独创性通路分析（IPA）对验证的RSS进行分析，以确定HPV（-）HNSCC中与放射敏感基因相关的典型通路、上游调节因子、疾病和功能以及基因网络。14个HNSCC细胞系在2戈伊照射后的存活分数为48%至72%。其中6个基因与辐射抗性呈正相关，35个基因与辐射抗性呈负相关。RSS在HPV（-）TCGA HNSCC队列（n = 203）中得到验证，发现放射抵抗组的无复发生存率（RFS）显著低于放射敏感组（p = 0.035）。细胞死亡和存活、细胞间信号传导和细胞运动在RSS中显著富集，并且RSS彼此高度相关。我们推导出HPV（-）HNSCC特异性RSS，并在独立队列中验证。通过分析HPV（-）伴HNSCC患者的RSS可以预测其辅助或确定性放疗的结果，这可能有助于制定个性化的治疗计划。
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. 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. 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. 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.