Meta-analysis of GLP1R, GIPR, ADCY3, and CREB1 expression in osteoarthritis identifies CREB1 as a potential biomarker and therapeutic target
Abstract
Background
Osteoarthritis (OA) is a progressive joint disease with no disease-modifying therapies. Incretin-related signaling pathways, including GLP1R, GIPR, ADCY3, and CREB1, may influence cartilage homeostasis and inflammation, but their transcriptional profiles across cohorts remain unclear. To evaluate the expression, diagnostic potential, and functional context of GLP1R, GIPR, ADCY3, and CREB1 in OA cartilage through an integrative meta-analysis of public transcriptomic datasets.
Methods
We systematically searched the GEO database, identifying 147 records. After screening and applying inclusion criteria, four datasets were included (GSE114007, GSE117999, GSE169077, GSE220243; total N = 83). Expression data were normalized within each dataset, converted to per-gene z-scores, and analyzed using random-effects meta-analysis. Machine learning classifiers (logistic regression, random forest, XGBoost) were trained with leave-one-dataset-out validation. Functional enrichment was performed using g:Profiler. Protocol registration: PROSPERO CRD420251177348.
Results
CREB1 (pooled mean difference +0.459, p = 0.036) and GLP1R (+0.518, p = 0.016) were significantly upregulated in OA cartilage, ADCY3 was downregulated (-0.552, p = 0.010), while GIPR showed no significant change. Heterogeneity was low (I2 = 0 % for CREB1, GLP1R, ADCY3). In classification, logistic regression achieved the highest pooled discrimination (AUC = 0.684), but performance varied across cohorts, indicating…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 83 participants or records.
Read the paper
Related studies
- Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
- A meta‐analysis of anal cancer incidence by risk group: Toward a unified anal cancer risk scale
- Global fertility in 204 countries and territories, 1950–2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021
- Exercise interventions in Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials
- Prognostic Significance of Carbonic Anhydrase IX Expression in Cancer Patients: A Meta-Analysis
- Glucocorticoid Resistance: Is It a Requisite for Increased Cytokine Production in Depression? A Systematic Review and Meta-Analysis
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.