Cis- and Trans-Acting Expression Quantitative Trait Loci of Long Non-Coding RNA in 2,549 Cancers With Potential Clinical and Therapeutic Implications

Frontiers in Oncology

Dan Wu¹  Zhong Wang²  Ziwei Wei²  Yun Zou²  Wenzhi Li²  Jintao Guo³  Chaoqun Xu³  Yudi Hu³  Hongkun Fang³  Ke Liu³  Ying Zhou³  Qiyuan Li³ 

[1] Department of Oncology, Xiamen the Fifth Hospital, Xiamen, China;Department of Urology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;School of Medicine, National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, China;

关键词: long non-coding RNA;    tumor immune microenvironment;    cancer;    instrumental variable analysis;    tumor infiltrating lymphocytes;    expression quantitative trait loci;   

DOI  :  10.3389/fonc.2020.602104

来源: DOAJ

【 摘 要 】

Many cancer risk loci act as expression quantitative trait loci (eQTLs) of transcripts including non-coding RNA. Long non-coding RNAs (lncRNAs) are implicated in various human cancers. However, the pathological and clinical impacts of the genetic determinants of lncRNAs in cancers remain largely unknown. In this study, we performed eQTL mapping of lncRNA expression (elncRNA) in 11 TCGA cancer types and characterized the biological processes of elncRNAs in the setting of genomic location, cancer treatment responses, and immune microenvironment. As a result, 10.86% of the cis-eQTLs and 1.67% of the trans-eQTLs of lncRNA were related to known genome-wide association studies (GWAS) cancer risk loci. The elncRNAs are significantly enriched for those which are previously annotated as predictive of drug sensitivities in cancer cell lines. We further revealed the downstream transcriptomic effectors of eQTL-elncRNA pairs. Our data specifically suggested that the genes affected by eQTL-elncRNA associations are enriched in the immune system processes and eQTL-elncRNA associations influence the constitution of tumor infiltrating lymphocytes. In ovarian cancer, the “rs34631313-AC092580.4” pair was associated with increased fraction of CD8+ T cells and M1 Macrophage; whereas in KIRC, the “rs9546285-LINC00426” pair was associated with increased fraction of CD8+ T cells and a decreased fraction of M2 macrophages. Our findings provide a systematic view of the transcriptomic impacts of the eQTL landscape of lncRNA in human cancers and suggest its strong potential relevance to cancer immunity and treatment.

【 授权许可】

Unknown