Downregulation of G Protein-Coupled Estrogen Receptor (GPER) is Associated with Reduced Prognosis in Patients with Gastric Cancer

Tian, Shan; Zhan, Na; Li, Ruixue; Dong, Weiguo

doi:10.12659/msm.913634

Cited by 24 publications

(32 citation statements)

References 40 publications

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“…Among the six energy metabolism-related genes, DYNC1I1, GPER1, MFAP2, C3, and GLI1 were risk factors while ARRB1 was a protective factor for clinical outcomes in GC. The prognostic value of the ve risk genes have been sporadically reported in previous studies, while the protective value of ARRB1 in GC was rarely identi ed [44][45][46][47][48][49]. Functional enrichment analysis revealed that this metabolism-related signature was signi cantly involved in some classical cancerrelated pathways.…”

Section: Discussionmentioning

confidence: 91%

Comprehensive Molecular Characterization and Identification of Prognostic Signature in Stomach Adenocarcinoma on The Basis of Energy-Metabolism-Related Genes

Chang

Wang

et al. 2021

Preprint

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Background: Stomach adenocarcinoma (STAD) is a leading cause of cancer deaths, but its molecular and prognostic characteristics has never been fully illustrated. Methods: We describe a comprehensive molecular evaluation of primary STAD based on comprehensive analysis of energy-metabolism-related gene (EMRG) expression profiles. Results: On the basis of 86 EMRGs that were significantly associated to patients’ progression-free survival (PFS), we propose a molecular classification dividing gastric cancer into two subtypes: Cluster 1, most of which are young patients and display more immune and stromal cell components in tumor microenvironment (TME) and lower tumor priority; and Cluster 2, which show early stages and better PFS. Moreover, we construct a 6-gene signature that can classify the prognostic risk of patients after a three-phase training, test and validation process. Compared with patients with low-risk score, patients with high risk score had shorter overall survival. Furthermore, calibration and DCA analysis plots indicate the excellent predictive performance of the 6-gene signature, and which present higher robustness and clinical usability compared with three previous reported prognostic gene signatures. According to gene set enrichment analysis (GSEA), gene sets related to the high-risk group were participated in the ECM receptor interaction and hedgehog signaling pathway.Conclusions: Identification of the EMRG-based molecular subtypes and prognostic gene model provides a roadmap for patient stratification and trials of targeted therapies.

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Section: Discussionmentioning

confidence: 91%

Comprehensive Molecular Characterization and Identification of Prognostic Signature in Stomach Adenocarcinoma on The Basis of Energy-Metabolism-Related Genes

Chang

Wang

et al. 2021

Preprint

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“…Among them, 33 articles were subsequently removed either because the data cannot be extracted, or the studies did not provide immunohistochemistry results. Finally, 20 articles were included in this meta-analysis [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. The characteristics of the included studies are shown in Table 6 .…”

Section: Resultsmentioning

confidence: 99%

Association between GPER gene polymorphisms and GPER expression levels with cancer predisposition and progression

Ulhaq

Soraya

Milliana

et al. 2021

Heliyon

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Estrogen is a female sex steroid hormone that plays a significant role in physiological functions. Evidence suggests that estrogen-signaling pathways are closely linked to cancer development and progression. The novel G protein-coupled estrogen receptor (GPER or GPR30) has been shown to influence cancer predisposition and progression, although results of related studies remain equivocal. Thus, this meta-analysis aimed to estimate the relationship between GPER gene polymorphisms and GPER expression levels, with cancer predisposition and progression. The pooled results showed that two GPER polymorphisms, rs3808350 and rs3808351, were significantly associated with cancer predisposition, especially in the Asian population, but no significant association was detected for rs11544331. In parallel, we also found that cancer aggressiveness and progression correlated with rs3808351 and GPER expression in cancerous tissues. Altogether, our findings suggest that GPER plays a pivotal role in cancer pathogenesis and progression. We suggest that rs3808350 and rs3808351 may be used as a prospective biomarker for cancer screening; while rs3808351 and GPER expression can be used to examine the prognosis of patients with cancer. Further biological studies are warranted to confirm our findings.

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“…Furthermore, bioinformatics data showed that GPER DNA promoter methylation may be involved in the reduced expression of GPER in GC and that GPER may act as a tumor suppressor through the regulation of the epithelial–mesenchymal transition (EMT) pathway. 76 Another study similarly indicated that GPER mRNA levels were significantly lower in GC tissues than in normal tissues, and a stage-dependent decrease was found in the GPER expression of GC on the basis of GPER fluorescence intensity in cancer stages I and II (45% and 30%) versus stages III and IV (25% and 20%, respectively). 77 The induction of pERK-dependent endoplasmic reticulum stress via GPER signaling may increase G1’s chemotherapeutic effect in the GC cells.…”

Section: Gper In Gastric Cancer (Gc)mentioning

confidence: 93%

“…Tian et al 76 demonstrated that GPER mRNA and protein levels were downregulated in GC tissues and cells, and the decreased expression of GPER protein was an independent risk factor for poor prognosis in patients with GC. Furthermore, bioinformatics data showed that GPER DNA promoter methylation may be involved in the reduced expression of GPER in GC and that GPER may act as a tumor suppressor through the regulation of the epithelial–mesenchymal transition (EMT) pathway.…”

Section: Gper In Gastric Cancer (Gc)mentioning

confidence: 99%

Role of G Protein-Coupled Estrogen Receptor in Digestive System Carcinomas: A Minireview

Qiu¹,

Xiong²,

Yu³

2021

OTT

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Digestive system carcinomas are one of the leading causes of cancer-related deaths worldwide. G protein-coupled estrogen receptor (GPER), a novel estrogen receptor, has been recognized as an important mediator in numerous cancer types. Recently, the function and clinical significance of GPER in digestive system carcinomas has been a subject of interest. Increasing evidence has revealed that GPER plays an important role as a potential biomarker in digestive system carcinomas. This work summarizes the recent literature and focuses on the emerging functional role of GPER in digestive system carcinomas, including gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. The potential application of GPER in novel strategies for the diagnosis and treatment of digestive system carcinomas is discussed and highlighted.

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Downregulation of G Protein-Coupled Estrogen Receptor (GPER) is Associated with Reduced Prognosis in Patients with Gastric Cancer

Cited by 24 publications

References 40 publications

Comprehensive Molecular Characterization and Identification of Prognostic Signature in Stomach Adenocarcinoma on The Basis of Energy-Metabolism-Related Genes

Comprehensive Molecular Characterization and Identification of Prognostic Signature in Stomach Adenocarcinoma on The Basis of Energy-Metabolism-Related Genes

Association between GPER gene polymorphisms and GPER expression levels with cancer predisposition and progression

Role of G Protein-Coupled Estrogen Receptor in Digestive System Carcinomas: A Minireview

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