GPER governs the immune infiltration of gastric cancer and activates the NF-κB/ROS/Apoptosis pathway in gastric mucosal epithelium

Yang, Xuefei; Zhang, Jiaqi; Ma, Junjun; Huang, Jinke; Wang, Yifan; Wang, Ping; Wang, Fengyun; Tang, Xudong

doi:10.1016/j.intimp.2023.110641

Cited by 5 publications

(4 citation statements)

References 28 publications

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“…In this investigation, we delved into the putative causative links between inflammatory mediators and the risk of gastric malignancy, leveraging an aggregation of extensive GWAS data alongside a two-sample Mendelian randomization framework. [ 45 , 46 ] Our findings reveal a dichotomy in the role of specific inflammatory mediators: the interleukin 6 receptor appears to mitigate the incidence of gastric malignancies, whereas the fatty acid binding protein 4 ostensibly augments this risk. [ 47 , 48 ] These results lend credence to the prognostic significance of inflammatory mediators concerning gastric malignancy within the context of GWAS data.…”

Section: Discussionmentioning

confidence: 99%

Exploring the association between inflammatory biomarkers and gastric cancer development: A two-sample mendelian randomization analysis.

Yang,

Lv,

et al. 2024

Medicine

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This study aimed to elucidate the potential causative links between inflammatory biomarkers and gastric cancer risk via a two-sample Mendelian randomization approach. Leveraging genome-wide association study (GWAS) data, we conducted a two-sample Mendelian randomization analysis. Instrumental variable selection for inflammatory markers – namely, tissue factor, monocyte chemotactic protein-1, E-selectin, interleukin 6 receptor, and fatty acid-binding protein 4 – was informed by SNP data from the IEU database. Strongly associated SNPs served as instrumental variables. We applied a suite of statistical methods, including Inverse Variance Weighted (IVW), Weighted Median Estimator (WME), MR-Egger, and mode-based estimates, to compute the odds ratios (ORs) that articulate the impact of these markers on gastric cancer susceptibility. The IVW method revealed that the interleukin 6 receptor was inversely correlated with gastric cancer progression (OR = 0.86, 95% CI = 0.74–0.99, P = .03), whereas fatty acid-binding protein 4 was found to elevate the risk (OR = 1.21, 95% CI = 1.05–1.39, P = .03). Instrumental variables comprised 5, 4, 7, 2, and 3 SNPs respectively. Convergent findings from WME, MR-Egger, and mode-based analyses corroborated these associations. Sensitivity checks, including heterogeneity, horizontal pleiotropy assessments, and leave-one-out diagnostics, affirmed the robustness and reliability of our instruments across diverse gastric malignancy tissues without substantial bias. Our research suggests that the interleukin 6 receptor potentially mitigates, while fatty acid-binding protein 4 may contribute to the pathogenesis of gastric cancer (GC). Unraveling the intricate biological interplay between inflammation and oncogenesis offers valuable insights for preemptive strategies and therapeutic interventions in gastric malignancy management.

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Section: Discussionmentioning

confidence: 99%

Exploring the association between inflammatory biomarkers and gastric cancer development: A two-sample mendelian randomization analysis.

Yang,

Lv,

et al. 2024

Medicine

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“…Decreased GPER in gastric cancer was associated with poor overall survival, progressionfree survival, and post-progression survival [97], while high expression was associated with better overall and disease-free survival, especially in female patients [99]. Contrary to this, other authors reported that tumors with increased GPER expression had worse overall survival [88].…”

Section: In Silico Studies Of Different Cancer Typesmentioning

confidence: 96%

“…In contrast, lower GPER expression has been demonstrated in breast, liver, lung, stomach, uterine, kidney, thyroid, gastric, and colorectal cancers compared to their healthy counterparts [90,[97][98][99][100]. Regarding survival rates and GPER expression, there are reports of both positive and negative correlations.…”

Section: In Silico Studies Of Different Cancer Typesmentioning

confidence: 99%

“…Several authors have conducted in silico analysis of information available in databases to reveal the involvement of GPER in the progression of various cancers. For this purpose, most of them used the cancer genome atlas (TCGA) [29,90,[96][97][98][99], gene expression omnibus (GEO) [97][98][99], European genome-phenome archive (EGA) [97], and oncomine [92,99] databases for GPER mRNA expression and human protein atlas [97] for GPER protein expression, as well as specific databases for breast (METABRIC) [96], stomach (TCGA-STAD) [99], and colon [100] cancer. The association between GPER mRNA expression and cancer prognosis was determined by Kaplan-Meier survival analysis [29,88,90,96,97,[99][100][101].…”

Section: In Silico Studies Of Different Cancer Typesmentioning

confidence: 99%

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The G Protein-Coupled Estrogen Receptor GPER in the Development and Progression of Cancer

Torres-López,

Olivas-Aguirre,

Dobrovinskaya

2024

Receptors

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The high incidence of cancer and the prevalence of chemoresistance are serious problems worldwide, underscoring the urgency of novel research focused on understanding the underlying mechanisms and finding new therapeutic targets. Recently, the G protein-coupled estrogen receptor (GPER) has received increasing attention, and it has been studied in various models, including physiological and pathological conditions, using appropriate pharmacological and molecular biological strategies. Numerous studies indicate that GPER plays an important role in cancer progression and resistance. This review focuses on the structure of GPER, the diversity of its ligands and GPER-activated signaling pathways, the role of GPER in cancer progression, and mechanisms of chemoresistance, with special emphasis on different cancer types and the tumor microenvironment. GPER was evidenced to exhibit conformational plasticity and different ligand binding modes. Therefore, GPER-mediated effects can be triggered by estrogens or various estrogen mimetics, including synthesized compounds, licensed drugs, or exogenous environmental compounds. We found multiple reports evidencing that GPER is differentially expressed in healthy tissues and tumors and plays a protumor role in breast, ovarian, lung, thyroid, and endometrial cancers. Additionally, there are several studies that indicate that GPER expression in cells of the tumor microenvironment may also contribute to cancer progression. Among the major mechanisms of GPER-mediated chemoresistance are the epithelial-mesenchymal transition, the overexpression of multidrug resistance pumps, and autophagy regulation.

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Advances in immune regulation of the G protein-coupled estrogen receptor

Dong,

Zeng,

et al. 2024

International Immunopharmacology

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GPER governs the immune infiltration of gastric cancer and activates the NF-κB/ROS/Apoptosis pathway in gastric mucosal epithelium

Cited by 5 publications

References 28 publications

Exploring the association between inflammatory biomarkers and gastric cancer development: A two-sample mendelian randomization analysis.

Exploring the association between inflammatory biomarkers and gastric cancer development: A two-sample mendelian randomization analysis.

The G Protein-Coupled Estrogen Receptor GPER in the Development and Progression of Cancer

Advances in immune regulation of the G protein-coupled estrogen receptor

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