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Activation of the cGAS-STING signaling pathway in adenomyosis patients
Yun Lin1, Luying Wang1, Mingzhu Ye1
1Department of Obstetrics and Gynecology, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan, China.
Objective:
Adenomyosis is characterized by the presence of endometrium or endometrium-like glands and stroma within the myometrium. In this study, we aimed to investigate whether the cGAS-STING pathway was activated and correlated with clinical outcomes in adenomyosis patients.
Materials And Methods:
Twenty patients diagnosed with adenomyosis and 10 patients diagnosed with cervical intraepithelial neoplasia grade 3 (CIN-3) but no adenomyosis were enrolled in this study. Specimens were collected during surgery from August 2017 to December 2017 at Third Xiangya Hospital. The messenger RNA (mRNA) and protein levels of key cGAS-STING pathway factors in uterine tissue were detected by real-time reverse-transcription polymerase chain reaction and immunohistochemistry, respectively. The correlations of gene expression and clinical outcomes, including dysmenorrhea and uterine volume, were analyzed.
Results:
The cGAS, STING, TANK-binding kinase 1 (TBK-1), interferon-α (IFN-α), IFN-β, and tumor necrosis factor-α (TNF-α) mRNA and protein levels in the ectopic endometrial tissue from adenomyosis patients were significantly higher compared with that from the controls in endometrium (p < .05). cGAS and STING gene expression were correlated with TBK-1, IFN-β, and TNF-α expression (p < .05). Importantly, TBK-1 and TNF-α expression were correlated with the clinical outcome of dysmenorrhea (p < .05).
Conclusion:
Our study reveals that the cGAS-STING pathway is activated in adenomyosis patients and its activation is subsequently correlated with clinical outcomes, which suggests that the cGAS-STING pathway may contribute to adenomyosis pathogenesis.
Insights
The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is activated in adenomyosis, correlating with disease severity and symptoms like dysmenorrhea. This suggests the pathway plays a role in adenomyosis development.
Area of Science:
- Gynecologic pathology
- Immunology
- Molecular biology
Background:
- Adenomyosis is a condition where endometrial tissue implants within the uterine myometrium.
- The role of innate immune pathways, such as the cGAS-STING pathway, in adenomyosis pathogenesis is not well understood.
Purpose of the Study:
- To investigate the activation status of the cGAS-STING pathway in adenomyosis.
- To explore the correlation between cGAS-STING pathway activation and clinical outcomes in adenomyosis patients.
Main Methods:
- Quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to measure mRNA and protein levels of cGAS-STING pathway components.
- Tissue samples from adenomyosis patients and controls were analyzed.
- Correlation analysis was performed between gene expression and clinical parameters like dysmenorrhea and uterine volume.
Main Results:
- Significantly elevated mRNA and protein levels of cGAS, STING, TANK-binding kinase 1 (TBK-1), interferon-α (IFN-α), IFN-β, and tumor necrosis factor-α (TNF-α) were observed in adenomyosis tissues compared to controls.
- cGAS and STING gene expression correlated with TBK-1, IFN-β, and TNF-α expression.
- TBK-1 and TNF-α expression levels were significantly correlated with the severity of dysmenorrhea.
Conclusions:
- The cGAS-STING pathway is activated in adenomyosis.
- Pathway activation is linked to clinical manifestations, particularly dysmenorrhea.
- The cGAS-STING pathway may be a key contributor to the pathogenesis of adenomyosis and a potential therapeutic target.
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