摘要
目的鉴定喉鳞状细胞癌(laryngeal squamous cell carcinoma,LSCC)患者生存相关的长链非编码RNA(long non-coding RNA,lncRNA)基因的单核苷酸多态性(single nucleotide polymorphism,SNP)位点。方法使用2000年1月-2012年12月在中国医学科学院肿瘤医院前期收集的98例患者样本,进行生存相关的全基因组关联研究(genome wide association study,GWAS),筛选出57个位于lncRNA基因上的多态位点。收集2009年1月-2018年3月解放军总医院、安徽医科大学第一附属医院和山东大学附属耳鼻喉医院的537例喉鳞状细胞癌患者样本,并在这些样本中验证初步筛选的57个多态位点。采用Sequenom MassARRAY基因分型平台进行基因分型。采用log-rank检验比较不同基因型患者的Kaplan-Meier生存曲线。通过多因素Cox回归比例风险模型计算不同基因型患者的死亡风险比(HR)及其95%CI。结果研究发现rs17059513、rs10208830和rs2901182与喉鳞状细胞癌患者总生存显著相关。与携带rs17059513 AA基因型患者相比,携带rs17059513 AG基因型的患者死亡风险增高[HR(95%CI)为2.23(1.46~3.39)];与携带rs10208830 GG基因型患者相比,携带rs10208830 CC基因型的患者死亡风险降低[HR(95%CI)为0.75(0.61~0.92)];与携带rs2901182 CC基因型患者相比,携带rs2901182 CT基因型的患者死亡风险增高[HR(95%CI)为2.10(1.11~4.00)]。多因素Cox回归加性模型分析显示rs17059513的HR(95%CI)为1.95(1.34~2.83),rs10208830的HR(95%CI)为0.77(0.63~0.93);显性模型分析显示rs17059513的HR(95%CI)为2.19(1.45~3.32),rs10208830的HR(95%CI)为0.74(0.56~0.98);隐性模型分析显示rs10208830的HR(95%CI)为1.59(1.10~2.30)。通过风险等位基因或风险基因型的累积分析,发现与生存相关的这3个多态位点具有联合效应。携带3个风险等位基因或携带2~3个风险基因型的患者死亡风险较高,HR(95%CI)分别为3.11(1.71~5.65)和3.24(1.97~5.32)。结论鉴定出3个新的与喉鳞状细胞癌患者预后密切相关的基�
Objective To identify single nucleotide polymorphisms(SNPs)in long non-coding RNA(LncRNA)that influences the survival of laryngeal squamous cell carcinoma(LSCC)patients.Methods We performed a genome wide association study(GWAS)on the survival of 98 LSCC patients who were previously recruited from the Cancer Hospital,the Chinese Academy of Medical Sciences from January 2000 to December 2012,and screened out 57 promising SNPs located in LncRNAs,which were replicated in the samples of 537 LSCC patients.The 537 LSCC patients were recruited from January 2009 to March 2018 in Chinese PLA General Hospital,the First Affiliated Hospital of Anhui Medical University and Shandong Provincial ENT Hospital.Genotyping analysis was performed using Sequenom MassARRAY system.The Kaplan-Meier survival curves of different genotypes were compared using log-rank tests.Hazard ratios(HRs)and their 95%confidence intervals(CIs)of the different genotypes were estimated through multivariate Cox proportional hazard models.Results The loci of rs17059513,rs10208830 and rs2901182 were significantly associated with the overall survival of LSCC patients.The risk of death in patients with rs17059513 AG genotype increased compared with rs17059513 AA genotype,with the HR(95%CI)being 2.23(1.46-3.39).The risk of death in patients with rs10208830 CC genotype was lower compared with rs10208830 GG genotype,with the HR(95%CI)being 0.75(0.61-0.92).The risk of death in patients with rs2901182 CT genotype increased compared with rs2901182 CC genotype,with the HR(95%CI)being 2.10(1.11-4.00).Multivariate Cox regression analysis revealed the HRs(95%CIs)of 1.95(1.34-2.83)for rs17059513 and 0.77(0.63-0.93)for rs10208830 using the additive model,the HRs(95%CIs)of 2.19(1.45-3.32)for rs17059513 and 0.74(0.56-0.98)for rs10208830 using the dominant model,and the HR(95%CI)of 1.59(1.10-2.30)for rs10208830 using the recessive model.We identified three SNPs having a joint effect on survival through accumulation of risk alleles or risk genotypes.Patients with 3 risk alleles
作者
杜忠礼
房忠菊
刘业海
朱玉华
陈立伟
孔欣茹
范俊达
任楠
徐伟
刘明波
DU Zhongli;FANG Zhongju;LIU Yehai;ZHU Yuhua;CHEN Liwei;KONG Xinru;FAN Junda;REN Nan;XU Wei;LIUMingbo(National Center for Clinical Laboratories,National Center of Gerontology,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing Hospital,Beijing 100730,China;Department of Otolaryngology,Weifang Medical University,Weifang 261053,Shandong Province,China;Department of Otorhinolaryngology,Head and Neck Surgery,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,Anhui Province,China;Department of Otolaryngology Head and Neck Surgery,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China;Department of Otolaryngology,Head and Neck Surgery,Hainan Hospital of Chinese PLA General Hospital,Sanya 572013,Hainan Province,China;Department of Otorhinolaryngology,Head and Neck Surgery,Shandong Provincial ENT Hospital Affiliated to Shandong University,Ji'nan 250021,Shandong Province,China)
出处
《解放军医学院学报》
CAS
2020年第6期614-618,633,共6页
Academic Journal of Chinese PLA Medical School
基金
海南省重点研发计划项目(ZDYF2017076)
关键词
单核苷酸多态性
长链非编码RNA
总生存
喉鳞状细胞癌
基因组学
single nucleotide polymorphisms
long non-coding RNA
overall survival
laryngeal squamous cell carcinoma
genomics
