Published online Dec 27, 2021. doi: 10.4240/wjgs.v13.i12.1708
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
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.
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.
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.
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.
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).
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.
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.