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基因变异与头颈部鳞状细胞癌的预后相关。

Genetic Variants Were Associated With the Prognosis of Head and Neck Squamous Carcinoma.

作者信息

He Yingzheng, Ji Pei, Li Yuancheng, Wang Ruixia, Ma Hongxia, Yuan Hua

机构信息

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.

Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.

出版信息

Front Oncol. 2020 Mar 20;10:372. doi: 10.3389/fonc.2020.00372. eCollection 2020.

Abstract

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. 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. 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, = 3.88 × 10; rs2641256 at 17p13.2: adjusted HR = 0.67, 95%CI = 0.56-0.80, = 7.51 × 10; rs2761591 at 11p13: adjusted HR = 2.07, 95%CI = 1.50-2.87, = 1.16 × 10; and rs854936 at 22q11.21: adjusted HR = 1.92, 95%CI = 1.43-2.57, = 1.27 × 10). 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 ( = 0.013) and ( = 0.047) in cancer tissues of TCGA, respectively. Our findings suggested that the SNPs (rs16879870, rs2641256, rs2761591, rs854936) might play a crucial role in prognosis of HNSCC.

摘要

作为全球第六大常见癌症,头颈癌(HNC)起源于口腔、咽和喉,且尚无强有力的预后生物标志物。尽管治疗方法有所改进,但数十年来头颈癌的5年生存率仍然相对较低。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。我们对261例头颈鳞状细胞癌(HNSCC)患者进行了全外显子组关联研究,然后在癌症基因组图谱(TCGA)数据库中使用Cox比例风险回归模型和Kaplan-Meier分析对生存情况进行验证。在合并两个阶段的结果后,4个SNP与HNSCC生存显著相关(6q14.3处的rs16879870:调整后HR = 2.02,95%CI = 1.50 - 2.73, = 3.88 × 10;17p13.2处的rs2641256:调整后HR = 0.67,95%CI = 0.56 - 0.80, = 7.51 × 10;11p13处的rs2761591:调整后HR = 2.07,95%CI = 1.50 - 2.87, = 1.16 × 10;22q11.21处的rs854936:调整后HR = 1.92,95%CI = 1.43 - 2.57, = 1.27 × 10)。此外,我们构建了一个受试者工作特征(ROC)模型来评估新的SNP与临床分期相结合在HNSCC预后中的预测效果(AUC = 0.715)。我们还发现,rs16879870和rs854936的基因型分别与TCGA癌症组织中基因( = 0.013)和( = 0.047)的表达显著相关。我们的研究结果表明,SNP(rs16879870、rs2641256、rs2761591、rs854936)可能在HNSCC预后中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c3d/7099049/2b7153e66cea/fonc-10-00372-g0001.jpg

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