Genetic Variants Were Associated With the Prognosis of Head and Neck Squamous Carcinoma
Genetic Variants Were Associated With the Prognosis of Head and Neck Squamous Carcinoma
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遗传变异与头颈鳞状细胞癌的预后相关
DOI：
10.3389/fonc.2020.00372
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发表时间：
2020-03-20
影响因子：
4.7
通讯作者：
Yuan, Hua
中科院分区：
文献类型：
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作者：
He, Yingzheng;Ji, Pei;Yuan, Hua
背景资料：头颈部恶性肿瘤（head and neck cancers，HNC）是世界上第六大常见的恶性肿瘤，多发生于口腔、咽喉部，目前尚无强有力的生物学标志物预测其预后。随着治疗的改善，HNC的5年生存率在几十年内仍然相对较低。单核苷酸多态性（SNP）在癌症预后中发挥作用的证据越来越多。研究方法：我们在261例头颈部鳞状细胞癌（HNSCC）患者中进行了一项外显子组范围的关联研究，然后通过使用考克斯比例风险回归模型和Kaplan-Meier分析在癌症基因组图谱（TCGA）数据库中验证生存率。结果如下：综合两阶段结果，4个SNPs与HNSCC生存率显著相关（rs 16879870在6q14.3：校正HR = 2.02，95%CI = 1.50-2.73，P = 3.88 × 10−6; rs 2641256在17p13.2：校正HR = 0.67，95%CI = 0.56-0.80，P = 7.51 × 10−6; 11 p13的rs 2761591：校正HR = 2.07，95%CI = 1.50-2.87，P = 1.16 × 10−5; 22q11.21的rs 854936：校正HR = 1.92，95%CI = 1.43-2.57，P = 1.27 × 10−5）。此外，我们构建了一个受试者工作特征（ROC）模型来估计新的SNPs结合临床分期对HNSCC预后的预测效果（AUC = 0.715）。rs 16879870和rs 854936基因型分别与GJB 7（P = 0.013）和RTN 4 R（P = 0.047）的表达显著相关。结论：rs 16879870、rs 2641256、rs 2761591、rs 854936单核苷酸多态性可能在HNSCC预后中起重要作用。
Background: As the sixth most common cancer of worldwide, head and neck cancers (HNC) are springing from oral cavity, pharynx and larynx and there is no strong biomarker for prognosis. Rates of 5 years survival with HNC remain relatively low in decades with improvement of treatments. Evidence that single nucleotide polymorphisms (SNPs) play a part in cancer prognosis is growing. Methods: We conducted an exome-wide association study among 261 patients with head and neck squamous cell carcinoma (HNSCC) and then validated in The Cancer Genome Atlas (TCGA) database for survival by using the Cox proportional hazards regression models and Kaplan–Meier analyses. Results: After combining the result of the two stages, 4 SNPs were significantly associated with HNSCC survival (rs16879870 at 6q14.3: adjusted HR = 2.02, 95%CI = 1.50–2.73, P = 3.88 × 10−6; rs2641256 at 17p13.2: adjusted HR = 0.67, 95%CI = 0.56–0.80, P = 7.51 × 10−6; rs2761591 at 11p13: adjusted HR = 2.07, 95%CI = 1.50–2.87, P = 1.16 × 10−5; and rs854936 at 22q11.21: adjusted HR = 1.92, 95%CI = 1.43–2.57, P = 1.27 × 10−5). Besides, we constructed a receiver operating characteristic (ROC) model to estimate predictive effect of the novel SNPs combined with clinical stage in HNSCC prognosis (AUC = 0.715). We also found the genotype of rs16879870 and rs854936 was significantly associated with the expression of gene GJB7 (P = 0.013) and RTN4R (P = 0.047) in cancer tissues of TCGA, respectively. Conclusion: Our findings suggested that the SNPs (rs16879870, rs2641256, rs2761591, rs854936) might play a crucial role in prognosis of HNSCC.