Yuan Jiapei, Tong Yang, Liu Xiaochuan, Li Mulin Jun, Zhang Qiang, Yang Yang
Department of Geriatrics, Tianjin Medical University General Hospital, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Center for Reproductive Medicine of Tianjin Medical University Second Hospital, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Int J Cancer. 2023 Jul 1;153(1):111-119. doi: 10.1002/ijc.34481. Epub 2023 Mar 3.
Enhancers are key regulatory elements that exert crucial roles in diverse biological processes, including tumorigenesis and cancer development. Active enhancers could produce transcripts termed enhancer RNAs (eRNAs), which could be used as an index of enhancer activity. Here, we present a versatile data portal, enhancer activity quantitative trait loci database (eaQTLdb; http://www.bioailab.com:3838/eaQTLdb), for exploring the effects of genetic variants on enhancer activity and prioritizing candidate variants across different cancer types. By leveraging the accumulated multiomics data, we systematically identified genetic variants which influence enhancer activity in different cancer types, termed as eaQTLs. We have linked the eaQTLs to hallmarks of cancer and patients' overall survival to illustrate their potential biological roles in cancer development and progression. Notably, eaQTLs associated with the infiltration abundance of 24 different immune cell types were identified and incorporated into eaQTLdb. In addition, we applied colocalization analyses to examine 59 complex diseases and traits to identify eaQTLs colocalized with diseases/traits GWAS signals. Overall, eaQTLdb, incorporating a rich resource for exploration of eaQTLs in different cancer types, will not only benefit users in prioritizing candidate genetic variants and enhancers, but also help researchers decipher the roles of eaQTLs in the dysregulated pathways of cancer and tumor immune microenvironment, opening new diagnostic and therapeutic avenues in precise medicine.
增强子是关键的调控元件,在包括肿瘤发生和癌症发展在内的多种生物学过程中发挥着至关重要的作用。活跃的增强子可产生被称为增强子RNA(eRNA)的转录本,其可作为增强子活性的指标。在此,我们展示了一个多功能数据门户——增强子活性数量性状位点数据库(eaQTLdb;http://www.bioailab.com:3838/eaQTLdb),用于探索遗传变异对增强子活性的影响,并对不同癌症类型中的候选变异进行优先级排序。通过利用积累的多组学数据,我们系统地鉴定了影响不同癌症类型中增强子活性的遗传变异,即eaQTL。我们将eaQTL与癌症特征和患者的总生存期联系起来,以阐明它们在癌症发展和进展中的潜在生物学作用。值得注意的是,我们鉴定了与24种不同免疫细胞类型的浸润丰度相关的eaQTL,并将其纳入eaQTLdb。此外,我们应用共定位分析来研究59种复杂疾病和性状,以鉴定与疾病/性状全基因组关联研究(GWAS)信号共定位的eaQTL。总体而言,eaQTLdb整合了丰富的资源用于探索不同癌症类型中的eaQTL,不仅将有助于用户对候选遗传变异和增强子进行优先级排序,还将帮助研究人员解读eaQTL在癌症失调通路和肿瘤免疫微环境中的作用,为精准医学开辟新的诊断和治疗途径。