Huang Ruixuan, Cho William C, Sun Yanni, Katie Chan Kei Hang
Annu Int Conf IEEE Eng Med Biol Soc. 2020 Jul;2020:2346-2352. doi: 10.1109/EMBC44109.2020.9176344.
Lung cancer is a major public health burden and among the highest incidence and mortality rates of the cancers. MicroRNAs (miRNAs) play an important role in the development of lung cancer. The aim of this study was to investigate whether there was a potential causal relation between miRNAs and non-small-cell lung cancer (NSCLC). 1,026 patients with NSCLC from The Cancer Genome Atlas (TCGA) were analyzed. NSCLC associated SNPs' allele scores were established, and candidate miRNAs were filtered from differential expression analysis. Mendelian randomization (MR) analysis was conducted for 5 candidate miRNA (hsa-miR-135b, hsa-miR-142, hsa-miR-182, hsa-miR-183 and hsa-miR-3607) and 76 candidate SNPs in lung adenocarcinoma (LUAD) group. According to the core assumptions of MR, there was no clear evidence of a causal relation between the 5 candidate miRNAs and LUAD. The reads per million miRNAs mapped (RPM) level of candidate miRNAs changed less than 3% per allele score. To our knowledge, this is the first study using the TCGA data set to investigate the causal relation between miRNAs and lung cancer using the MR approach, and also one of the first MR studies to use miRNA expression as an exposure factor, with the SNPs as instrumental variables.
肺癌是一项重大的公共卫生负担，在各类癌症中发病率和死亡率位居前列。微小RNA（miRNA）在肺癌发展过程中发挥着重要作用。本研究旨在调查miRNA与非小细胞肺癌（NSCLC）之间是否存在潜在因果关系。对来自癌症基因组图谱（TCGA）的1026例NSCLC患者进行了分析。建立了与NSCLC相关的单核苷酸多态性（SNP）的等位基因评分，并通过差异表达分析筛选出候选miRNA。对肺腺癌（LUAD）组中的5个候选miRNA（hsa-miR-135b、hsa-miR-142、hsa-miR-182、hsa-miR-183和hsa-miR-3607）和76个候选SNP进行了孟德尔随机化（MR）分析。根据MR的核心假设，没有明确证据表明这5个候选miRNA与LUAD之间存在因果关系。每个等位基因评分中，候选miRNA的每百万映射miRNA读数（RPM）水平变化小于3%。据我们所知，这是第一项使用TCGA数据集通过MR方法研究miRNA与肺癌之间因果关系的研究，也是最早将miRNA表达作为暴露因素、以SNP作为工具变量的MR研究之一。
