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
Abstract
BACKGROUND

Ghrelin is an adipokine that plays an important role in energy balance. Expression of ghrelin and ghrelin receptor has been investigated in different tissues and tumors. Studies regarding expression of ghrelin and ghrelin receptor in colorectal tumors are scarce and no data on expression of ghrelin and its receptor in colorectal adenomas has been published. Ghrelin and ghrelin receptor were highly expressed in colon carcinoma cells while expression was decreased in less differentiated tumors, presuming that ghrelin might be important in early phases of tumorigenesis.

AIM

To investigate the expression of ghrelin and ghrelin receptor in human colorectal adenomas and adjacent colorectal tissue.

METHODS

In this prospective study (conducted from June 2015 until May 2019) we included 92 patients (64 male and 28 female) who underwent polypectomy for colorectal adenomas in the Department of Gastroenterology and Hepatology, “Sestre milosrdnice” Clinical Hospital Center in Zagreb, Croatia. After endoscopic removal of colorectal adenoma, an additional sample of colon mucosa in the proximity of the adenoma was collected for 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 (ab150514, ABCAM Inc, Cambridge, United States) and ghrelin receptor (ab48285, ABCAM Inc, Cambridge, United States). Categorical and nominal variables were described through frequencies and proportions and the difference between specific groups were analyzed with Fisher’s and Fisher-Freeman-Halton’s method respectively. Spearman's rank correlation coefficient was determined for correlation of expression of ghrelin and ghrelin receptor in adenoma and adjacent colon tissue with the grade of adenoma dysplasia.

RESULTS

Among 92 patients with colorectal adenoma 43 had adenomas with high-grade dysplasia (46.7%). 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).

CONCLUSION

Ghrelin and ghrelin receptor are expressed in colorectal adenoma and adjacent tissue with ghrelin expression being more pronounced in high grade dysplasia as a possible consequence of increased local synthesis.

Keywords: Ghrelin; Ghrelin receptor; Adipokines; Colorectal adenoma; Colorectal adenoma dysplasia; Large intestine

Core Tip: Colorectal adenomas are benign, but premalignant lesions of the large intestine, as dysplasia may progress over time and result in the occurrence of colorectal carcinoma. The risk of progression is increased in adenomas with high-grade dysplasia. There are several risk factors for adenomas with high-grade dysplasia, of which energy imbalance and metabolic syndrome are increasing in importance because of their rising prevalence. Ghrelin is an adipokine important in energy balance and its expression was investigated in different tumors and tissues. With this prospective observational study we gained new insight on the expression and role of ghrelin and ghrelin receptor in colorectal adenomas.