Identification and characterization of two consistent osteoarthritis subtypes by transcriptome and clinical data integration.
Rheumatology (Oxford)
; 60(3): 1166-1175, 2021 03 02.
Article
in En
| MEDLINE
| ID: mdl-32885253
ABSTRACT
OBJECTIVE:
To identify OA subtypes based on cartilage transcriptomic data in cartilage tissue and characterize their underlying pathophysiological processes and/or clinically relevant characteristics.METHODS:
This study includes n = 66 primary OA patients (41 knees and 25 hips), who underwent a joint replacement surgery, from which macroscopically unaffected (preserved, n = 56) and lesioned (n = 45) OA articular cartilage were collected [Research Arthritis and Articular Cartilage (RAAK) study]. Unsupervised hierarchical clustering analysis on preserved cartilage transcriptome followed by clinical data integration was performed. Protein-protein interaction (PPI) followed by pathway enrichment analysis were done for genes significant differentially expressed between subgroups with interactions in the PPI network.RESULTS:
Analysis of preserved samples (n = 56) resulted in two OA subtypes with n = 41 (cluster A) and n = 15 (cluster B) patients. The transcriptomic profile of cluster B cartilage, relative to cluster A (DE-AB genes) showed among others a pronounced upregulation of multiple genes involved in chemokine pathways. Nevertheless, upon investigating the OA pathophysiology in cluster B patients as reflected by differentially expressed genes between preserved and lesioned OA cartilage (DE-OA-B genes), the chemokine genes were significantly downregulated with OA pathophysiology. Upon integrating radiographic OA data, we showed that the OA phenotype among cluster B patients, relative to cluster A, may be characterized by higher joint space narrowing (JSN) scores and low osteophyte (OP) scores.CONCLUSION:
Based on whole-transcriptome profiling, we identified two robust OA subtypes characterized by unique OA, pathophysiological processes in cartilage as well as a clinical phenotype. We advocate that further characterization, confirmation and clinical data integration is a prerequisite to allow for development of treatments towards personalized care with concurrently more effective treatment response.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Messenger
/
Osteoarthritis, Hip
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Osteoarthritis, Knee
/
Gene Expression Profiling
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Aged
/
Female
/
Humans
/
Male
Language:
En
Journal:
Rheumatology (Oxford)
Journal subject:
REUMATOLOGIA
Year:
2021
Document type:
Article
Affiliation country:
Países Bajos