Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Dec 27, 2021; 13(12): 1708-1720
Published online Dec 27, 2021. doi: 10.4240/wjgs.v13.i12.1708
Expression of adipokine ghrelin and ghrelin receptor in human colorectal adenoma and correlation with the grade of dysplasia
Sanja Stojsavljevic-Shapeski, Lucija Virovic-Jukic, Davor Tomas, Marko Duvnjak, Vedran Tomasic, Davor Hrabar, Dominik Kralj, Ivan Budimir, Neven Barsic, Neven Ljubicic
Sanja Stojsavljevic-Shapeski, Lucija Virovic-Jukic, Vedran Tomasic, Davor Hrabar, Dominik Kralj, Ivan Budimir, Neven Barsic, Neven Ljubicic, Division of Gastroenterology, Department of Internal Medicine, «Sestre Milosrdnice» University Hospital Center, Zagreb 10000, Croatia
Lucija Virovic-Jukic, Marko Duvnjak, Davor Hrabar, Neven Barsic, Neven Ljubicic, Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
Davor Tomas, Ljudevit Jurak Department of Pathology, «Sestre Milosrdnice» University Hospital Center, Zagreb 10000, Croatia
Davor Tomas, Department of Pathology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
Author contributions: Stojsavljevic-Shapeski S, Virovic-Jukic L and Tomas D designed the study; Stojsavljevic-Shapeski S, Tomasic V, Kralj D, Barsic N, Budimir I and Hrabar D participated in the acquisition of data; Stojsavljevic-Shapeski S, Virovic-Jukic L and Tomas D participated in the analysis and interpretation of the data; Stojsavljevic-Shapeski S and Virovic-Jukic L drafted the initial manuscript; Hrabar D, Duvnjak M and Ljubicic N revised the article critically for important intellectual content.
Institutional review board statement: The study and all its documents as well as the informed consent form were reviewed and approved by the Ethical committee of «Sestre Milosrdnice» University Hospital Center, 10000 Zagreb, Croatia in December 2013.
Informed consent statement: All study participants, or their legal guardian, provided after extensive written and communicated information an informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Sanja Stojsavljevic-Shapeski, MD, PhD, Senior Research Fellow, Division of Gastroenterology, Department of Internal Medicine, «Sestre Milosrdnice» University Hospital Center, Vinogradska ul. 29, Zagreb 10000, Croatia. sanja.stojsavljevic@kbcsm.hr
Received: June 28, 2021
Peer-review started: June 28, 2021
First decision: July 27, 2021
Revised: August 20, 2021
Accepted: November 3, 2021
Article in press: November 3, 2021
Published online: December 27, 2021
Processing time: 178 Days and 14 Hours
ARTICLE HIGHLIGHTS
Research background

Ghrelin is an adipokine that influences energy expenditure and appetite, modulates gastric motility, secretion of gastric acid, pancreatic endocrine function and has an important role in glucose metabolism, insulin resistance and metabolic syndrome. Metabolic syndrome is one of the known risk factors for colorectal carcinoma development, and both diseases have had a significant rise in prevalence. Colorectal adenomas are premalignant lesions that can with time progress to colorectal carcinoma, and have also been linked to metabolic syndrome. Ghrelin, as one of the links between metabolic syndrome and tumor progression, has been investigated in several tissues and tumors but current data are not sufficient for complete understanding of all ghrelin effects.

Research motivation

Researching the published data regarding influence of ghrelin and its receptor in colorectal carcinoma and colorectal adenoma progression, we realized that there is a need for further insight on the subject since data on this topic is lacking. Current guidelines on colorectal adenoma and carcinoma screening and postpolypectomy surveillance do not focus on the presence of metabolic syndrome or any of its components. Obtaining more insight into the link between metabolic syndrome and colorectal adenoma and carcinoma occurrence could possibly in future influence new guidelines.

Research objectives

We aimed to investigate the expression of ghrelin and ghrelin receptor in colorectal adenomas and adjacent colorectal tissue to give a new perspective on this problem.

Research methods

We conducted a prospective study (from June 2015 until May 2019) that included 92 patients who underwent polypectomy for colorectal adenomas in the Department of Gastroenterology and Hepatology, “Sestre milosrdnice” Clinical Hospital Center in Zagreb, Croatia. An additional sample of colon mucosa was collected in the proximity of the removed colorectal adenoma for further pathohistological analysis. Adenomas were graded according to the stage of dysplasia, and ghrelin and ghrelin receptor expression were determined immunohistochemically in both adenoma and adjacent colon tissue using the polyclonal antibody for ghrelin and ghrelin receptor.

Research results

High expression of ghrelin was 7 times more common in high-grade adenoma compared to low-grade adenomas (13.95% to 2.04%, P = 0.048), while the expression of ghrelin in adjacent colon tissue was low. We found no correlation between ghrelin receptor expression in adenoma and adjacent colon tissue and the grade of colorectal adenoma dysplasia. The most significant correlation was found between ghrelin and ghrelin receptor expression in adenomas with high-grade dysplasia (rho = 0.519, P < 0.001).

Research conclusions

Our study is the first to show that ghrelin and ghrelin receptor are expressed in colorectal adenomas and adjacent tissue. We found that ghrelin expression was more pronounced in adenomas with high-grade dysplasia compared to those with low-grade dysplasia. The results of this study underline the importance of ghrelin in progression of dysplasia in colorectal adenoma but there is a need for further studies to determine the expression of different subtypes of ghrelin receptors in colorectal adenomas and exact ghrelin receptors role.

Research perspectives

Ghrelin and metabolic syndrome role in general need to be adequately investigated in colorectal adenoma progression since we are experiencing an epidemic of colorectal carcinoma intertwined with an epidemic of obesity. We believe that obtaining more insight into this problem could help us to better understand the dysplasia progression pathways, influence the surveillance programs and guidelines, and in that way ensure early recognition of patients in greater risk for colorectal carcinoma development.