Genetic, Pharmacogenomic, and Immune Landscapes of Enhancer RNAs Across Human Cancers.

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Abstract

Enhancer RNAs (eRNA) regulate gene expression and play critical roles in cancer. Using large-scale omics data from The Cancer Genome Atlas (TCGA), we systematically investigated the impact of genetic variants on eRNA expression and identified approximately 1 million eRNA quantitative trait loci (eRNA-QTL) as cis- and trans-acting. Over 16,000 eRNA-QTLs were associated with patient overall survival. Assessing the impact of eRNAs on more than 1,000 imputed anticancer drug responses across approximately 10,000 patients with cancer revealed more than 7 million significant associations. Furthermore, approximately 240,000 significant associations were identified between eRNA expression and immune cell abundance deconvoluted by TIMER, CIBERSORT, ImmuCellAI, and ImmuneCellGSVA. Finally, a user-friendly data portal was generated: Genetic, Pharmacogenomic, and Immune Landscapes of eRNAs (GPIeR; https://hanlab.tamhsc.edu/GPIeR/). GPIeR is a large-scale multidimensional data portal that can be used to explore eRNA-associated genetic variants, drug responses, and immune infiltration, with the purpose of facilitating functional and clinical investigations of eRNAs in cancer.

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Journal

Journal ID (iso-abbrev): Cancer Res

Title: Cancer research

Publisher: American Association for Cancer Research (AACR)

ISSN (Electronic): 1538-7445

ISSN (Print): 0008-5472

Publication date (Electronic): Mar 01 2022

Volume: 82

Issue: 5

Affiliations

[1 ] MOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

[2 ] Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas.

[3 ] Center for Artificial Intelligence Biology, Hubei Bioinformatics & Molecular Imaging Key Laboratory, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

[4 ] Center for Epigenetics and Disease Prevention, Institute of Biosciences and Technology, Texas A&M University, Houston, Texas.

[5 ] Department of Computer Science, Rice University, Houston, Texas.

[6 ] Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

[7 ] Department of Translational Medical Sciences, College of Medicine, Texas A&M University, Houston, Texas.

Article

Publisher Item ID: 0008-5472.CAN-21-2058

DOI: 10.1158/0008-5472.CAN-21-2058

PubMed ID: 35022213

SO-VID: 308a34dd-8a55-47df-8585-41db9950edbb

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