iTRAQ-based quantitative proteomics reveals biomarkers/pathways in psoriasis that can predict the efficacy of methotrexate.
Options
Date of Publication
October 2022
Publication Type
Article
Division/Institute
Author
Yan, Kexiang | |
Meng, Qian | |
He, Han | |
Zhu, Hongwen | |
Wang, Zhicheng | |
Han, Ling | |
Huang, Qiong | |
Zhang, Zhenghua | |
Zhou, Hu | |
Xu, Jinhua |
Subject(s)
Series
Journal of the European Academy of Dermatology and Venereology : JEADV
ISSN or ISBN (if monograph)
1468-3083
Publisher
Wiley
Language
English
Publisher DOI
PubMed ID
35666151
Description
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.
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.