Steinberg, J., Southam, L., Fontalis, A. orcid.org/0000-0001-5547-288X et al. (8 more authors) (2021) Linking chondrocyte and synovial transcriptional profile to clinical phenotype in osteoarthritis. Annals of the Rheumatic Diseases, 80 (8). pp. 1070-1074. ISSN 0003-4967
Abstract
Objectives: To determine how gene expression profiles in osteoarthritis joint tissues relate to patient phenotypes and whether molecular subtypes can be reproducibly captured by a molecular classification algorithm.
Methods: We analysed RNA sequencing data from cartilage and synovium in 113 osteoarthritis patients, applying unsupervised clustering and Multi-Omics Factor Analysis to characterise transcriptional profiles. We tested the association of the molecularly defined patient subgroups with clinical characteristics from electronic health records.
Results: We detected two patient subgroups in low-grade cartilage (showing no/minimal degeneration, cartilage normal/softening only), with differences associated with inflammation, extracellular matrix-related and cell adhesion pathways. The high-inflammation subgroup was associated with female sex (OR 4.12, p=0.0024) and prescription of proton pump inhibitors (OR 4.21, p=0.0040). We identified two independent patient subgroupings in osteoarthritis synovium: one related to inflammation and the other to extracellular matrix and cell adhesion processes. A seven-gene classifier including MMP13, APOD, MMP2, MMP1, CYTL1, IL6 and C15orf48 recapitulated the main axis of molecular heterogeneity in low-grade knee osteoarthritis cartilage (correlation ρ=−0.88, p<10−10) and was reproducible in an independent patient cohort (ρ=−0.85, p<10−10).
Conclusions: These data support the reproducible stratification of osteoarthritis patients by molecular subtype and the exploration of new avenues for tailored treatments.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 Mar 2022 15:53 |
Last Modified: | 23 Mar 2022 15:53 |
Status: | Published |
Publisher: | BMJ |
Refereed: | Yes |
Identification Number: | 10.1136/annrheumdis-2020-219760 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:184970 |
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