Chen Haimiao, Wang Ting, Huang Shuiping, Zeng Ping
Department of Epidemiology and Biostatistics, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China.
Center for Medical Statistics and Data Analysis, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China.
J Cancer. 2021 Jan 1;12(3):840-848. doi: 10.7150/jca.47918. eCollection 2021.
Although genome-wide association studies (GWAS) have successfully identified multiple genetic variants associated with cervical cancer, the functional role of those variants is not well understood. To bridge such gap, we integrated the largest cervical cancer GWAS ( = 9,347) with gene expression measured in six human tissues to perform a multi-tissue transcriptome-wide association study (TWAS). We identified a total of 20 associated genes in the European population, especially four novel non-MHC genes (i.e. , , and ). Further, we attempted to validate our results in another independent cervical cancer GWAS from the East Asian population ( = 3,314) and re-discovered four genes including , , and . In our subsequent co-expression analysis, we discovered and were co-expressed in TCGA tumor samples and showed both and were enriched in "plasma membrane". Using the protein-protein interaction analysis we observed strong interactions between the proteins produced by genes that are associated with cervical cancer. Overall, our study identified multiple candidate genes, especially four non-MHC genes, which may be causally associated with the risk of cervical cancer. However, further investigations with larger sample size are warranted to validate our findings in diverse populations.
尽管全基因组关联研究（GWAS）已成功鉴定出多个与宫颈癌相关的基因变异，但这些变异的功能作用尚不清楚。为了填补这一空白，我们将最大规模的宫颈癌GWAS（n = 9347）与在六种人体组织中测量的基因表达进行整合，以开展多组织转录组全关联研究（TWAS）。我们在欧洲人群中总共鉴定出20个相关基因，尤其是四个新的非MHC基因（即，，和）。此外，我们试图在另一个来自东亚人群的独立宫颈癌GWAS（n = 3314）中验证我们的结果，并重新发现了四个基因，包括，，和。在我们随后的共表达分析中，我们发现和在TCGA肿瘤样本中共表达，并且显示和均在“质膜”中富集。使用蛋白质-蛋白质相互作用分析，我们观察到与宫颈癌相关的基因所产生的蛋白质之间存在强烈的相互作用。总体而言，我们的研究鉴定出多个候选基因，尤其是四个非MHC基因，它们可能与宫颈癌风险存在因果关系。然而，需要进一步开展更大样本量的研究，以在不同人群中验证我们的发现。
