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      Ghrelin and its role in gastrointestinal tract tumors

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          Abstract

          Ghrelin, an orexigenic hormone, is a peptide that binds to the growth hormone secretagogue receptor; it is secreted mainly by enteroendocrine cells in the oxyntic glands of the stomach. Ghrelin serves a role in both local and systemic physiological processes, and is implicated in various pathologies, including neoplasia, with tissue expression in several types of malignancies in both in vitro and in vivo studies. However, the precise implications of the ghrelin axis in metastasis, invasion and cancer progression regulation has yet to be established. In the case of gastrointestinal (GI) tract malignancies, ghrelin has shown potential to become a prognostic factor or even a therapeutic target, although data in the literature are inconsistent and unsystematic, with reports untailored to a specific histological subtype of cancer or a particular localization. The evaluation of immunohistochemical expression shows a limited outlook owing to the low number of cases analyzed, and in vivo analyses have conflicting data regarding differences in ghrelin serum levels in patients with cancer. The aim of this review was to examine the relationship between ghrelin and GI tract malignancies to demonstrate the inconsistencies in current results and to highlight its clinical significance in the outcome of these patients.

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          Ghrelin is a growth-hormone-releasing acylated peptide from stomach.

          Small synthetic molecules called growth-hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through GHS-R, a G-protein-coupled receptor for which the ligand is unknown. Recent cloning of GHS-R strongly suggests that an endogenous ligand for the receptor does exist and that there is a mechanism for regulating GH release that is distinct from its regulation by hypothalamic growth-hormone-releasing hormone (GHRH). We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. The purified ligand is a peptide of 28 amino acids, in which the serine 3 residue is n-octanoylated. The acylated peptide specifically releases GH both in vivo and in vitro, and O-n-octanoylation at serine 3 is essential for the activity. We designate the GH-releasing peptide 'ghrelin' (ghre is the Proto-Indo-European root of the word 'grow'). Human ghrelin is homologous to rat ghrelin apart from two amino acids. The occurrence of ghrelin in both rat and human indicates that GH release from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin.
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            A receptor in pituitary and hypothalamus that functions in growth hormone release.

            Small synthetic molecules termed growth hormone secretagogues (GHSs) act on the pituitary gland and the hypothalamus to stimulate and amplify pulsatile growth hormone (GH) release. A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. On the basis of its pharmacological and molecular characterization, this GPC-R defines a neuroendocrine pathway for the control of pulsatile GH release and supports the notion that the GHSs mimic an undiscovered hormone.
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              Systemic immune-inflammation index for predicting prognosis of colorectal cancer

              AIM To investigate the clinical significance of preoperative systemic immune-inflammation index (SII) in patients with colorectal cancer (CRC). METHODS A retrospective analysis of 1383 cases with CRC was performed following radical surgery. SII was calculated with the formula SII = (P × N)/L, where P, N, and L refer to peripheral platelet, neutrophil, and lymphocyte counts, respectively. The clinicopathological features and follow-up data were evaluated to compare SII with other systemic inflammation-based prognostic indices such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in patients with CRC. RESULTS The optimal cut-off point for SII was defined as 340. The overall survival (OS) and disease-free survival (DFS) were better in patients with low NLR, PLR, and SII (P < 0.05). The SII was an independent predictor of OS and DFS in multivariate analysis. The area under the receiver-operating characteristics (ROC) curve for SII (0.707) was larger than those for NLR (0.602) and PLR (0.566). In contrast to NLR and PLR, SII could effectively discriminate between the TNM subgroups. CONCLUSION SII is a more powerful tool for predicting survival outcome in patients with CRC. It might assist the identification of high-risk patients among patients with the same TNM stage.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                September 2021
                19 July 2021
                19 July 2021
                : 24
                : 3
                : 663
                Affiliations
                [1 ]Department of Pathology, ‘Grigore T. Popa’ University of Medicine and Pharmacy, Iași 700115, Romania
                [2 ]Department of Histology, ‘Grigore T. Popa’ University of Medicine and Pharmacy, Iași 700115, Romania
                Author notes
                Correspondence to: Dr Irene Alexandra Spiridon, Department of Pathology, ‘Grigore T. Popa’ University of Medicine and Pharmacy, 16 University Street, Iași 700115, Romania, E-mail: spiridon.irene@ 123456umfiasi.ro
                Article
                MMR-0-0-12302
                10.3892/mmr.2021.12302
                8335721
                34296307
                275583be-66e5-408a-a682-34e6105e4012
                Copyright: © Spiridon et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 11 April 2021
                : 23 June 2021
                Categories
                Review

                ghrelin,growth hormone secretagogue receptor,carcinogenesis,cancer,pathology,prognosis

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