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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Overexpression of G protein-coupled receptor 31 as a poor prognosticator in human colorectal cancer
Yu-Ming Rong, Xiao-Ming Huang, De-Jun Fan, Xu-Tao Lin, Feng Zhang, Jian-Cong Hu, Ying-Xin Tan, Xi Chen, Yi-Feng Zou, Ping Lan
Yu-Ming Rong, VIP Region, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
Xiao-Ming Huang, Department of Hepatobiliary Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
Xiao-Ming Huang, De-Jun Fan, Xu-Tao Lin, Jian-Cong Hu, Ying-Xin Tan, Xi Chen, Yi-Feng Zou, Ping Lan, Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
De-Jun Fan, Xu-Tao Lin, Department of Gastrointestinal Endoscopy, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
Feng Zhang, Department of Rheumatology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
Jian-Cong Hu, Ying-Xin Tan, Xi Chen, Yi-Feng Zou, Ping Lan, Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
Author contributions: Rong YM, Huang XM and Fan DJ contributed equally to this paper. Rong YM, Huang XM, Fan DJ and Lin XT performed the majority of experiments and analyzed the data; Zhang F, Hu JC, Tan YX and Chen X collected the clinicopathological data and tissue of patients; Huang XM, Zou YF and Lan P designed and coordinated the research; Rong YM, Fan DJ and Lin XT wrote the paper; Huang XM, Zhang F and Zou YF revised the paper.
Supported by National Key Clinical Discipline; and the Medical Scientific Research Foundation of Guangdong Province, No. A2016198; and the Science and Technology Planning Project of Guangdong Province, No. 20160916, No. 2015B020229001 and No. 2014SC111.
Institutional review board statement: Our research was based on resources from our database and specimen library and it did not involve human or animal subjects. Thus, the approval of institutional review board was waived.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The ARRIVE guidelines have been adopted in this study.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yi-Feng Zou, MD, PhD, Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Road, Guangzhou 510655, Guangdong Province, China. zouyif@mail.sysu.edu.cn
Telephone: +86-13719225862 Fax: +86-20-38254009
Received: August 8, 2018
Peer-review started: August 9, 2018
First decision: August 24, 2018
Revised: September 13, 2018
Accepted: October 5, 2018
Article in press: October 5, 2018
Published online: November 7, 2018
ARTICLE HIGHLIGHTS
Research background
G protein-coupled receptor 31 (GPR31) plays an important role in a variety of physiological and pathological processes, including inflammation and tumor progression. In this present study, we aimed to elucidate the association between the expression level of GPR31 and colorectal cancer (CRC) progression.
Research motivation
12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] plays an important role in cancer promotion. It potentially acts through GPR31. We aimed to elucidate the association between the expression level of GPR31 and CRC progression. We expect GPR 31 as one of reliable biomarkers can provide guidance to the treatment of CRC and help predict treatment prognosis.
Research objectives
GPR31 is a critical prognostic factor of overall survival and disease-free survival in CRC patients and is closely related to the occurrence, development and prognosis of CRC. GPR31 may become a novel biomarker and therapeutic target for CRC.
Research methods
We obtained paraffin-embedded pathological specimens from 466 CRC patients. And we examined GPR31 expression levels in CRC tissues from two independent cohorts via immunohistochemical staining. All patients were categorized into either the GPR31 low expression group or GPR31 high expression group. The clinicopathological factors and the prognosis of patients in the GPR31 low expression group and GPR31 high expression group were compared.
Research results
Results of the present study showed that GPR31 expression in colorectal cancer tissue was significantly higher than that in normal mucosa and that GPR31 expression levels are closely related to distant metastasis of tumors, which are consistent with findings reported in previous studies. Further univariate and multivariate analyses showed that patients with high GPR31 expression had a worse prognosis and decreased overall survival and disease-free survival than patients that exhibited low GPR31 expression.
Research conclusions
We found that GPR31 was closely related to the occurrence, development, and prognosis of CRC. And GPR31 may become a novel biomarker and therapeutic target for CRC. Although few studies have discussed the role of GPR31 in tumors, it is reasonable to believe that GPR31 plays a key regulatory role in tumor development and progression by mediating a specific “switch” effect by 12(S)-HETE. Further studies are warranted to elucidate the detailed mechanisms underlying GPR31 function, specifically the molecular mechanisms by which GPR31 expression affects carcinogenesis process, such as tumor proliferation, differentiation, migration and invasion in CRC.
Research perspectives
High GPR31 expression levels were found to be correlated with pM classification of CRC and to serve as an independent predictive factor of poor survival of CRC patients. Further in vivo and in vitro experiments should be done to elucidate the molecular mechanisms by which GPR31 expression affects carcinogenesis process, such as tumor proliferation, differentiation, migration and invasion in CRC.
