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      Double role of depression in gastric cancer: As a causative factor and as consequence

      editorial

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          Abstract

          In this editorial we comment on the article “Hotspots and frontiers of the relationship between gastric cancer and depression: A bibliometric study”. Gastric cancer (GC) is a common malignancy in the digestive system with increased mortality and morbidity rates globally. Standard treatments, such as gastrectomy, negatively impact patients' quality of life and beyond the physical strain, GC patients face psychological challenges, including anxiety and depression. The prevalence of depression can be as high as 57%, among gastrointestinal cancer patients. Due to the advancements in treatment effectiveness and increased 5-year overall survival rates, attention has shifted to managing psychological effects. However, the significance of managing the depression doesn’t lie solely in the need for a better psychological status. Depression leads to chronic stress activating the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, leading release of catecholamines inducing tumor proliferation, migration, and metastasis, contributing to GC progression. The dysregulation of neurotransmitters and the involvement of various signaling pathways underscore the complex interplay between depression and GC. Comprehensive strategies are required to address the psychological aspects of GC, including region-specific interventions and increased monitoring for depression. Understanding the intricate relationship between depression and GC progression is essential for developing effective therapeutic strategies and improving overall outcomes for patients facing this complex disease. In this Editorial we delve into double role of depression in the pathogenesis of GC and as a complication of it.

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          Most cited references15

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          Prevalence, associations, and adequacy of treatment of major depression in patients with cancer: a cross-sectional analysis of routinely collected clinical data

          Major depression is an important complication of cancer. However, reliable data are lacking for the prevalence of depression in patients with cancer in different primary sites, the association of depression with demographic and clinical variables within cancer groupings, and the proportion of depressed patients with cancer receiving potentially effective treatment for depression. We investigated these questions with data from a large representative clinical sample.
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            Novel regulatory program for norepinephrine-induced epithelial–mesenchymal transition in gastric adenocarcinoma cell lines

            Norepinephrine and epinephrine, catecholamine hormones that are major mediators for chronic stress-induced cancers, are implicated in the progression of a number of cancer cells, including gastric adenocarcinoma. However, the underlying mechanisms of these hormones have not been well elucidated. Epithelial–mesenchymal transition (EMT) is a crucial event responsible for cancer cell invasion and metastasis. The hypothesis regarding whether the promotive effects of norepinephrine (NE) on cancer are in part due to its ability to induce an EMT program has not been proven. In this study, we show that NE does not only obviously induce EMT alterations in the morphological characteristics of gastric adenocarcinoma cells, but also increases the markers of EMT, including vimentin expression, and decreases E-cadherin expression, further resulting in cell motility and invasiveness. We also reveal that these actions are mainly mediated through the activation of β2-AR–HIF-1α–Snail signaling pathways. In summary, this study implies that NE induces EMT in gastric adenocarcinoma through the regulation of β2-AR–HIF-1α–Snail activity. The data provide a new perspective on chronic stress in a negative social and psychological state, which may be a risk factor for cancer development and progression. EMT: a novel regulatory program for stress hormone norepinephrine. EMT and gastric adenocarcinoma.
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              Isoprenaline induces epithelial-mesenchymal transition in gastric cancer cells.

              The emerging role of stress-related signaling in regulating cancer development and progression has been recognized. However, whether stress serves as a mechanism to promote gastric cancer metastasis is not clear. Here, we show that the β2-AR agonist, isoprenaline, upregulates expression levels of CD44 and CD44v8-10 in gastric cancer cells. CD44, a cancer stem cell-related marker, is expressed at high levels in gastric cancer tissues, which strongly correlates with the occurrence of epithelial-mesenchymal transition (EMT)-associated phenotypes both in vivo and in vitro. Combined with experimental observations in two human gastric cancer cell lines, we found that β2-AR signaling can initiate EMT. It led to an increased expression of mesenchymal markers, such as α-SMA, vimentin, and snail at mRNA and protein levels, and conversely a decrease in epithelial markers, E-cadherin and β-catenin. Isoprenaline stimulation of β2-AR receptors activates the downstream target STAT3, which functions as a positive regulator and mediated the phenotypic switch toward a mesenchymal cell type in gastric cancer cells. Our data provide a mechanistic understanding of the complex signaling cascades involving stress-related hormones and their effects on EMT. In light of our observations, pharmacological interventions targeting β2-AR-STAT3 signaling can potentially be used to ameliorate stress-associated influences on gastric cancer development and progression.
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                Author and article information

                Contributors
                Journal
                World J Gastroenterol
                World J Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                14 March 2024
                14 March 2024
                : 30
                : 10
                : 1266-1269
                Affiliations
                Department of General Surgery, University Hospital of Larissa, Larissa 41110, Greece. gregsurg@ 123456yahoo.gr
                Department of General Surgery, University Hospital of Larissa, Larissa 41110, Greece
                Department of General Surgery, University Hospital of Larissa, Larissa 41110, Greece
                Author notes

                Author contributions: Christodoulidis G, Konstantinos-Eleftherios K and Marina-Nektaria K contributed to this paper; Christodoulidis G designed the overall concept and outline of the manuscript; Christodoulidis G, Konstantinos-Eleftherios K and Marina-Nektaria K contributed to the discussion and design of the manuscript; Christodoulidis G, Konstantinos-Eleftherios K and Marina-Nektaria K contributed to the writing, editing the manuscript, and review of literature.

                Corresponding author: Grigorios Christodoulidis, MD, PhD, Surgeon, Department of General Surgery, University Hospital of Larissa, Mezourlo, Larissa 41110, Greece. gregsurg@ 123456yahoo.gr

                Article
                jWJG.v30.i10.pg1266 90877
                10.3748/wjg.v30.i10.1266
                11000075
                38596492
                fbbb9b46-ef47-466e-9101-add712e167b4
                ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.

                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: https://creativecommons.org/Licenses/by-nc/4.0/

                History
                : 16 December 2023
                : 13 January 2024
                : 23 February 2024
                Categories
                Editorial

                gastric cancer,depression,anxiety,chronic stress,pathogenesis of gastric cancer

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