iTRAQ-based quantitative proteomics reveals biomarkers/pathways in psoriasis that can predict the efficacy of methotrexate.

Yan, Kexiang; Meng, Qian; He, Han; Zhu, Hongwen; Wang, Zhicheng; Han, Ling; Huang, Qiong; Zhang, Zhenghua; Yawalkar, Nikhil; Zhou, Hu; Xu, Jinhua (2022). iTRAQ-based quantitative proteomics reveals biomarkers/pathways in psoriasis that can predict the efficacy of methotrexate. Journal of the European Academy of Dermatology and Venereology : JEADV, 36(10), pp. 1784-1795. Wiley 10.1111/jdv.18292

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BACKGROUND

Methotrexate (MTX) is the first-line medicine to treat psoriasis. So far, there has been less research on protein biomarkers to predict its efficacy by the proteomic technique.

OBJECTIVES

To evaluate differentially expressed proteins in peripheral mononuclear cells (PBMCs) between good responders (GRs) and non-responders (NRs) after MTX treatment, compared with normal controls (NCs).

METHODS

We quantified protein expression of PBMCs with 4 GRs and 4 NRs to MTX and 4 NCs by isobaric tags for relative and absolute quantification (iTRAQ), analyzing and identifying proteins related to efficacy of MTX in 18 psoriatic patients.

RESULTS

A total of 3,177 proteins had quantitative information, and 403 differentially expressed proteins (fold change ≥ 1.2, p < .05) were identified. Compared to NCs, upregulated proteins (ANXA6, RPS27A, EZR, XRCC6), participating in the activation of NF-κB, the JAK-STAT pathway, and neutrophil degranulation were detected in GRs. The proteins (GPV, FN1, STOM), involving platelet activation, signaling and aggregation as well as neutrophil degranulation were significantly downregulated in GRs. These proteins returned to normal levels after MTX treatment. Furthermore, Western blotting identified the expression of ANXA6 and STAT1 in PBMCs, which were significantly downregulated in GRs, but not in NRs.

CONCLUSIONS

We identified seven differentially expressed and regulated proteins (ANXA6, GPV, FN1, XRCC6, STOM, RPS27A, and EZR) as biomarkers to predict MTX efficacy in NF-κB signaling, JAK-STAT pathways, neutrophil degranulation, platelet activation, signaling and aggregation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology

UniBE Contributor:

Yawalkar, Nikhil

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1468-3083

Publisher:

Wiley

Language:

English

Submitter:

Pubmed Import

Date Deposited:

08 Jun 2022 07:42

Last Modified:

05 Dec 2022 16:20

Publisher DOI:

10.1111/jdv.18292

PubMed ID:

35666151

URI:

https://boris.unibe.ch/id/eprint/170458

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