Expression of adipokine ghrelin and ghrelin receptor in human colorectal adenoma and correlation with the grade of dysplasia

摘要

BACKGROUNDGhrelin is an adipokine that plays an important role in energy balance. Expressionof ghrelin and ghrelin receptor has been investigated in different tissues andtumors. Studies regarding expression of ghrelin and ghrelin receptor in colorectaltumors are scarce and no data on expression of ghrelin and its receptor incolorectal adenomas has been published. Ghrelin and ghrelin receptor werehighly expressed in colon carcinoma cells while expression was decreased in lessdifferentiated tumors, presuming that ghrelin might be important in early phasesof tumorigenesis.AIMTo investigate the expression of ghrelin and ghrelin receptor in human colorectaladenomas and adjacent colorectal tissue.METHODSIn this prospective study (conducted from June 2015 until May 2019) we included92 patients (64 male and 28 female) who underwent polypectomy for colorectaladenomas in the Department of Gastroenterology and Hepatology, “Sestre milosrdnice” Clinical Hospital Center in Zagreb, Croatia. After endoscopicremoval of colorectal adenoma, an additional sample of colon mucosa in theproximity of the adenoma was collected for pathohistological analysis. Adenomaswere graded according to the stage of dysplasia, and ghrelin and ghrelin receptorexpression were determined immunohistochemically in both adenoma andadjacent colon tissue using the polyclonal antibody for ghrelin (ab150514,ABCAM Inc, Cambridge, United States) and ghrelin receptor (ab48285, ABCAMInc, Cambridge, United States). Categorical and nominal variables were describedthrough frequencies and proportions and the difference between specific groupswere analyzed with Fisher’s and Fisher-Freeman-Halton’s method respectively.Spearman's rank correlation coefficient was determined for correlation ofexpression of ghrelin and ghrelin receptor in adenoma and adjacent colon tissuewith the grade of adenoma dysplasia.RESULTSAmong 92 patients with colorectal adenoma 43 had adenomas with high-gradedysplasia (46.7%). High expression of ghrelin was 7 times more common in highgradeadenoma 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 nocorrelation between ghrelin receptor expression in adenoma and adjacent colontissue and the grade of colorectal adenoma dysplasia. The most significantcorrelation was found between ghrelin and ghrelin receptor expression inadenomas with high-grade dysplasia (rho = 0.519, P < 0.001).CONCLUSIONGhrelin and ghrelin receptor are expressed in colorectal adenoma and adjacenttissue with ghrelin expression being more pronounced in high grade dysplasia asa possible consequence of increased local synthesis.