Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

An Integrated Pan-Cancer Analysis and Structure-Based Virtual Screening of GPR15

Yanjing Wang
ORCID logo ,
Xiangeng Wang
ORCID logo ,
Yi Xiong
ORCID logo ,
Cheng‐Dong Li
,
Qin Xu
,
Lu Shen
,
Aman Chandra Kaushik
* ,
Dong-Qing Wei
* ORCID logo
Version 1 : Received: 21 July 2019 / Approved: 23 July 2019 / Online: 23 July 2019 (11:15:19 CEST)

A peer-reviewed article of this Preprint also exists.

Wang, Y.; Wang, X.; Xiong, Y.; Li, C.-D.; Xu, Q.; Shen, L.; Chandra Kaushik, A.; Wei, D.-Q. An Integrated Pan-Cancer Analysis and Structure-Based Virtual Screening of GPR15. Int. J. Mol. Sci. 2019, 20, 6226. Wang, Y.; Wang, X.; Xiong, Y.; Li, C.-D.; Xu, Q.; Shen, L.; Chandra Kaushik, A.; Wei, D.-Q. An Integrated Pan-Cancer Analysis and Structure-Based Virtual Screening of GPR15. Int. J. Mol. Sci. 2019, 20, 6226.

Abstract

G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan GPCR involving HIV infection, colonic inflammation and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability of inhibiting cancer cell growth. However, no study reported the potential role of GPR15 in a pan-cancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) than in normal tissues. And among 33 cancer types, GPR15 expression is significantly correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), lung adenocarcinoma (LUAD) positively and stomach adenocarcinoma (STAD) negatively. This study also revealed that commonly upregulated gene set in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted the structure-based virtual screening. The top 8 hits compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provided novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15 antagonists.

Keywords

GPR15, pan-cancer, TCGA, cancer immunity, differential gene expression, prognosis, virtual screening

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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