目的 分析探究长链非编码核糖核酸(LncRNAs)与肺鳞癌放疗效果的关系。方法 以LncRNAs为暴露因素,肺鳞癌放疗效果为结局事件,采用两样本孟德尔随机化分析方法,对从全基因组关联研究(GWAS)数据库中获取的LncRNAs和肺鳞癌放疗的GWAS数据集分析LncRNAs与肺鳞癌放疗效果的孟德尔随机化关联性。以逆方差加权法(IVW)为主要分析方法,以MR-Egger回归、加权中位数法(WME)、简单模式(SM)和加权模式(WM)为次要分析方法,并通过异质性检验和敏感性分析来确保结果的稳健性和可靠性。结果 IVW分析结果显示,基因间长链非编码核糖核酸00261(LncRNA linc00261)(OR=0.442,95%CI:0.245~0.799)是肺鳞癌放疗无效的保护因素(P<0.05),LncRNA HOX转录反义RNA(HOTAIR)(OR=1.768,95%CI:1.050~2.978)、LncRNA H19(OR=1.749,95%CI:1.324~2.310)是肺鳞癌放疗无效的危险因素(P<0.05),且MR-Egger、WME、SM、WM分析的β与IVW的β方向一致。Cochran′s Q异质性检验结果显示,LncRNA HOTAIR、LncRNA linc00261、LncRNA H19的SNPs均未发现异质性存在(P>0.05);MR Egger回归的截距项分析结果显示,上述3种LncRNAs的SNPs中均未检测到水平多效性(P>0.05);孟德尔随机多效性残差和离群值(MR-PRESSO)法分析结果显示,与上述3种LncRNAs高度相关的SNPs不存在离群值(P＞0.05);“留一法”敏感性分析结果显示,逐一剔除与肺鳞癌放疗效果强相关的上述3种LncRNAs的SNPs后,两样本孟德尔随机化分析结果无明显改变。结论 LncRNA linc00261是肺鳞癌放疗无效的保护因素,降低肺鳞癌放疗无效风险,而LncRNA HOTAIR、LncRNA H19是肺鳞癌放疗无效的危险因素,增加肺鳞癌放疗无效风险。
Abstract
Objective To explore the relationship between long-chain non-coding ribonucleic acids (LncRNAs) and radiotherapy efficacy of lung squamous cell carcinoma. Methods LncRNAs were used as the exposure factor, and the radiotherapy effect of lung squamous cell carcinoma was used as the outcome event. Two-sample Mendelian randomization analysis method was adopted to analyze the Mendelian randomization association between LncRNAs and the radiotherapy effect of lung squamous cell carcinoma from the GWAS datasets obtained from the genome wide association studies (GWAS) database. The inverse variance weighting method (IVW) was used as the main analysis method, and MR-Egger regression, weighted median estimator (WME), simple model (SM) and weighted model (WM) were used as the secondary analysis methods. Heterogeneity test and sensitivity analysis were conducted to ensure the robustness and reliability of the results. Results The IVW analysis showed that long chain non-coding ribonucleic acid large intergenic noncoding 00261 (LncRNA linc00261) (OR=0.442, 95% CI: 0.245-0.799) was a protective factor for the ineffective radiotherapy of lung squamous cell carcinoma (P<0.05), LncRNA HOX anti-sense RNA (HOTAIR) (OR=1.768, 95%CI: 1.050-2.978), and LncRNA H19 (OR=1.749, 95%CI: 1.324-2.310) were risk factors for the ineffective radiotherapy of lung squamous cell carcinoma (P<0.05), and the β values analyzed by MR Egger, WME, SM, and WM were consistent with that of IVW. The Cochran’s Q heterogeneity test showed that there was no heterogeneity in the SNPs of LncRNA HOTAIR, LncRNA linc00261, and LncRNA H19 (P>0.05). The intercept analysis of MR Egger regression showed that no horizontal pleiotropy was detected in the SNPs of the above three LncRNAs(P>0.05). The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method analysis showed that there were no outliers in SNPs highly correlated with the three LncRNAs mentioned above(P>0.05). The sensitivity analysis results of the "leave one method" showed that after removing the SNPs of the three LncRNAs strongly related to the radiotherapy effect of lung squamous cell carcinoma one by one, there was no significant change in the two-sample Mendelian randomization analysis results. Conclusions LncRNA linc00261 is a protective factor for the ineffective radiotherapy of lung squamous cell carcinoma, reducing the risk of ineffective radiotherapy, while LncRNA HOTAIR and LncRNA H19 are risk factors for the ineffective radiotherapy of lung squamous cell carcinoma, increasing the risk of ineffective radiotherapy.
关键词
长链非编码核糖核酸 /
肺鳞癌 /
放疗 /
孟德尔随机化分析
Key words
long chain non-coding ribonucleic acid /
lung squamous cell carcinoma /
radiotherapy /
Mendelian randomization analysis
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