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

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

  • Int Immunopharmacol. 2023 Jul 22;122:110641. doi: 10.1016/j.intimp.2023.110641.
Xuefei Yang 1 Jiaqi Zhang 2 Jing Ma 2 Jinke Huang 2 Yifan Wang 3 Ping Wang 2 Fengyun Wang 2 Xudong Tang 4
Affiliations

Affiliations

  • 1 Department of Integration of Chinese and Western Medicine, Peking University Health Science Center (xiyuan), Beijing, China; Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China; Department of Gastroenterology, Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), Beijing, China.
  • 2 Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China.
  • 3 Department of Integration of Chinese and Western Medicine, Peking University Health Science Center (xiyuan), Beijing, China; Department of Gastroenterology, Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), Beijing, China.
  • 4 Department of Integration of Chinese and Western Medicine, Peking University Health Science Center (xiyuan), Beijing, China; Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China; Department of Gastroenterology, Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), Beijing, China.. Electronic address: txdly@sina.com.
Abstract

Background: Gastric Cancer (GC) is with high mortality and morbidity. The GC morbidity of males is twice as high as that of females. G-protein Estrogen Receptor (GPER) bears on this phenomenon.

Methods: Networks and experiments assessed the GPER expression in different validity and content. The evidence-based practice involved accessing the clinical relevance of GPER by UALCAN and Kaplan-Meier plotter. Enrichment analyses contributed to guide further experimental validations. Activation of the NF-κB/ROS/Apoptosis pathway was analyzed by WB, immunofluorescence (IF), microplate reader and flow cytometry. TISIDB and TIMER identified the immune infiltration investigations, with credibility boosted by the Kaplan-Meier plotter.

Results: The appraisers revealed that GPER significantly decreased in GC at both gene and protein levels with highly approved prognosis value (P < 0.05). GPER was a significant fate determinant governing the inner part of gastric glands. NF-κB pathway and the following ROS in gastric cells were activated after MNU stimulation (20 μM, 24 h), and the GPER antagonist G15 strengthened the effect of MNU. Furthermore, GPER expression positively correlated with immune cells and various immune markers in GC patients, with highly approved clinical relevance. For example, type-2 helper cells enriched GC patients had a lower survival rate in the GPER-high expression group (P < 0.05).

Conclusion: We demonstrated that GPER governs the GC progression by activating the NF-κB/ROS/Apoptosis pathway in gastric cells and regulating the immune environment around them.

Keywords

Apoptosis; G-protein estrogen receptor; Gastric cancer; Immune infiltration; NF-κB pathway.

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