Skip to main content
Erschienen in: Clinical Rheumatology 4/2022

12.11.2021 | Original Article

Machine learning to identify immune-related biomarkers of rheumatoid arthritis based on WGCNA network

verfasst von: Yulan Chen, Ruobing Liao, Yuxin Yao, Qiao Wang, Lingyu Fu

Erschienen in: Clinical Rheumatology | Ausgabe 4/2022

Einloggen, um Zugang zu erhalten

Abstract

Objectives

This study was designed to identify the potential diagnostic biomarkers of rheumatoid arthritis (RA) and to explore the potential pathological relevance of immune cell infiltration in this disease.

Methods

Three previously published datasets containing gene expression data from 35 RA patients and 29 controls (GSE55235, GSE55457, and GSE12021) were downloaded from the GEO database, after which a weighted correlation network analysis (WGCNA) approach was utilized to clarify differentially abundant genes. Candidate biomarkers of RA were then identified via the use of a LASSO regression model and support vector machine recursive feature elimination (SVM-RFE) analyses. Data were validated based upon the area under the receiver operating characteristic curve (AUC) values, with hub genes being identified as those with an AUC > 85% and a P value < 0.05. Lastly, the CIBERSORT algorithm was used to assess immune cell infiltration of RA tissues, and correlations between immune cell infiltration and disease-related diagnostic biomarkers were assessed.

Results

The green–yellow module containing 87 genes was found to be highly correlated with RA positivity. FADD, CXCL2, and CXCL8 were identified as potential RA diagnostic biomarkers (AUC > 0.85), and these results were validated using the GSE77298 dataset. Immune cell infiltration analyses revealed the expression of hub genes to be correlated with mast cells, monocytes, activated NK cells, CD8 T cells, resting dendritic cells, and plasma cells.

Conclusion

These data indicate that FADD, CXCL2, and CXCL8 are valuable diagnostic biomarkers of RA, offering new insight that can guide future studies of RA incidence and progression.
Key Points
Using the WGCNA approach and machine learning analyses to identify the hub genes in 64 samples.
Identifying the hub genes FADD, CXCL2, and CXCL8 as RA diagnostic biomarkers and confirming it in validation data.
Assessing the immune infiltration of RA tissues and correlations between hub genes and immune infiltration by CIBERSORT algorithm.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
4.
Zurück zum Zitat Courvoisier DS, Chatzidionysiou K, Mongin D, Lauper K, Mariette X, Morel J, Gottenberg JE, Bergstra SA, Suarez MP, Codreanu C, Kvien TK, Santos MJ, Pavelka K, Hetland ML, Askling J, Turesson C, Kubo S, Tanaka Y, Iannone F, Choquette D, Nordström DC, Rotar Z, Lukina G, Gabay C, Van Vollenhoven R, Finckh A (2021) The impact of seropositivity on the effectiveness of biologic anti-rheumatic agents: results from a collaboration of 16 registries. Rheumatology (Oxford) 60(2):820–828. https://doi.org/10.1093/rheumatology/keaa393CrossRef Courvoisier DS, Chatzidionysiou K, Mongin D, Lauper K, Mariette X, Morel J, Gottenberg JE, Bergstra SA, Suarez MP, Codreanu C, Kvien TK, Santos MJ, Pavelka K, Hetland ML, Askling J, Turesson C, Kubo S, Tanaka Y, Iannone F, Choquette D, Nordström DC, Rotar Z, Lukina G, Gabay C, Van Vollenhoven R, Finckh A (2021) The impact of seropositivity on the effectiveness of biologic anti-rheumatic agents: results from a collaboration of 16 registries. Rheumatology (Oxford) 60(2):820–828. https://​doi.​org/​10.​1093/​rheumatology/​keaa393CrossRef
5.
16.
20.
25.
Zurück zum Zitat Blanco FJ, Möricke R, Dokoupilova E, Codding C, Neal J, Andersson M, Rohrer S, Richards H (2017) Secukinumab in active rheumatoid arthritis: a phase III randomized, double-blind, active comparator- and placebo-controlled study. Arthritis Rheumatol (Hoboken, N.J.) 69(6):1144–1153. https://doi.org/10.1002/art.40070CrossRef Blanco FJ, Möricke R, Dokoupilova E, Codding C, Neal J, Andersson M, Rohrer S, Richards H (2017) Secukinumab in active rheumatoid arthritis: a phase III randomized, double-blind, active comparator- and placebo-controlled study. Arthritis Rheumatol (Hoboken, N.J.) 69(6):1144–1153. https://​doi.​org/​10.​1002/​art.​40070CrossRef
33.
Zurück zum Zitat Zhang HW, Wang Q, Mei HX, Zheng SX, Ali AM, Wu QX, Ye Y, Xu HR, Xiang SY, Jin SW (2019) RvD1 ameliorates LPS-induced acute lung injury via the suppression of neutrophil infiltration by reducing CXCL2 expression and release from resident alveolar macrophages. Int Immunopharmacol 76105877. https://doi.org/10.1016/j.intimp.2019.105877 Zhang HW, Wang Q, Mei HX, Zheng SX, Ali AM, Wu QX, Ye Y, Xu HR, Xiang SY, Jin SW (2019) RvD1 ameliorates LPS-induced acute lung injury via the suppression of neutrophil infiltration by reducing CXCL2 expression and release from resident alveolar macrophages. Int Immunopharmacol 76105877. https://​doi.​org/​10.​1016/​j.​intimp.​2019.​105877
36.
Zurück zum Zitat Wiegand P, Lupu L, Hüttmann N, Wack J, Rawer S, Przybylski M, Schmitz K (2020) Epitope identification and affinity determination of an inhibiting human antibody to interleukin IL8 (CXCL8) by SPR- biosensor-mass spectrometry combination. J Am Soc Mass Spectrom 31(1):109–116. https://doi.org/10.1021/jasms.9b00050CrossRefPubMed Wiegand P, Lupu L, Hüttmann N, Wack J, Rawer S, Przybylski M, Schmitz K (2020) Epitope identification and affinity determination of an inhibiting human antibody to interleukin IL8 (CXCL8) by SPR- biosensor-mass spectrometry combination. J Am Soc Mass Spectrom 31(1):109–116. https://​doi.​org/​10.​1021/​jasms.​9b00050CrossRefPubMed
37.
Zurück zum Zitat Kienhorst LB, van Lochem E, Kievit W, Dalbeth N, Merriman ME, Phipps-Green A, Loof A, van Heerde W, Vermeulen S, Stamp LK, van Koolwijk E, de Graaf J, Holzinger D, Roth J, Janssens HJ, Merriman TR, Broen JC, Janssen M, Radstake TR (2015) Gout is a chronic inflammatory disease in which high levels of interleukin-8 (CXCL8), myeloid-related protein 8/myeloid-related protein 14 complex, and an altered proteome are associated with diabetes mellitus and cardiovascular disease. Arthritis Rheumatol (Hoboken, N.J.) 67(12):3303–3313. https://doi.org/10.1002/art.39318CrossRef Kienhorst LB, van Lochem E, Kievit W, Dalbeth N, Merriman ME, Phipps-Green A, Loof A, van Heerde W, Vermeulen S, Stamp LK, van Koolwijk E, de Graaf J, Holzinger D, Roth J, Janssens HJ, Merriman TR, Broen JC, Janssen M, Radstake TR (2015) Gout is a chronic inflammatory disease in which high levels of interleukin-8 (CXCL8), myeloid-related protein 8/myeloid-related protein 14 complex, and an altered proteome are associated with diabetes mellitus and cardiovascular disease. Arthritis Rheumatol (Hoboken, N.J.) 67(12):3303–3313. https://​doi.​org/​10.​1002/​art.​39318CrossRef
39.
Zurück zum Zitat Krishnamurthy A, Joshua V, Haj Hensvold A, Jin T, Sun M, Vivar N, Ytterberg AJ, Engström M, Fernandes-Cerqueira C, Amara K, Magnusson M, Wigerblad G, Kato J, Jiménez-Andrade JM, Tyson K, Rapecki S, Lundberg K, Catrina SB, Jakobsson PJ, Svensson C, Malmström V, Klareskog L, Wähämaa H, Catrina AI (2016) Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis 75(4):721–729. https://doi.org/10.1136/annrheumdis-2015-208093CrossRefPubMed Krishnamurthy A, Joshua V, Haj Hensvold A, Jin T, Sun M, Vivar N, Ytterberg AJ, Engström M, Fernandes-Cerqueira C, Amara K, Magnusson M, Wigerblad G, Kato J, Jiménez-Andrade JM, Tyson K, Rapecki S, Lundberg K, Catrina SB, Jakobsson PJ, Svensson C, Malmström V, Klareskog L, Wähämaa H, Catrina AI (2016) Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis 75(4):721–729. https://​doi.​org/​10.​1136/​annrheumdis-2015-208093CrossRefPubMed
41.
Zurück zum Zitat Schubert N, Dudeck J, Liu P, Karutz A, Speier S, Maurer M, Tuckermann J, Dudeck A (2015) Mast cell promotion of T cell-driven antigen-induced arthritis despite being dispensable for antibody-induced arthritis in which T cells are bypassed. Arthritis Rheumatol (Hoboken, N.J.) 67(4):903–913. https://doi.org/10.1002/art.38996CrossRef Schubert N, Dudeck J, Liu P, Karutz A, Speier S, Maurer M, Tuckermann J, Dudeck A (2015) Mast cell promotion of T cell-driven antigen-induced arthritis despite being dispensable for antibody-induced arthritis in which T cells are bypassed. Arthritis Rheumatol (Hoboken, N.J.) 67(4):903–913. https://​doi.​org/​10.​1002/​art.​38996CrossRef
Metadaten
Titel
Machine learning to identify immune-related biomarkers of rheumatoid arthritis based on WGCNA network
verfasst von
Yulan Chen
Ruobing Liao
Yuxin Yao
Qiao Wang
Lingyu Fu
Publikationsdatum
12.11.2021
Verlag
Springer International Publishing
Erschienen in
Clinical Rheumatology / Ausgabe 4/2022
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-021-05960-9

Weitere Artikel der Ausgabe 4/2022

Clinical Rheumatology 4/2022 Zur Ausgabe

Letters of Biomedical and Clinical Research

UBA1 gene mutation in giant cell arteritis

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.