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Derlin-1, as a Potential Early Predictive Biomarker for Nonresponse to Infliximab Treatment in Rheumatoid Arthritis, Is Related to Autophagy

BACKGROUND: The goal of this study was to identify potential predictive biomarkers for the therapeutic effect of infliximab (IFX) in Rheumatoid arthritis (RA) and explore the potential molecular mechanism of nonresponse to IFX treatment to achieve individualized treatment of RA. METHODS: Differentia...

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Autores principales: Cai, Yongsong, Xu, Ke, Aihaiti, Yirixiati, Li, Zhijin, Yuan, Qiling, Xu, Jing, Zheng, Haishi, Yang, Mingyi, Wang, Bo, Yang, Yanni, Yang, Yin, Xu, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762214/
https://www.ncbi.nlm.nih.gov/pubmed/35046954
http://dx.doi.org/10.3389/fimmu.2021.795912
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author Cai, Yongsong
Xu, Ke
Aihaiti, Yirixiati
Li, Zhijin
Yuan, Qiling
Xu, Jing
Zheng, Haishi
Yang, Mingyi
Wang, Bo
Yang, Yanni
Yang, Yin
Xu, Peng
author_facet Cai, Yongsong
Xu, Ke
Aihaiti, Yirixiati
Li, Zhijin
Yuan, Qiling
Xu, Jing
Zheng, Haishi
Yang, Mingyi
Wang, Bo
Yang, Yanni
Yang, Yin
Xu, Peng
author_sort Cai, Yongsong
collection PubMed
description BACKGROUND: The goal of this study was to identify potential predictive biomarkers for the therapeutic effect of infliximab (IFX) in Rheumatoid arthritis (RA) and explore the potential molecular mechanism of nonresponse to IFX treatment to achieve individualized treatment of RA. METHODS: Differential gene expression between IFX responders and nonresponders in the GSE58795 and GSE78068 datasets was identified. Coexpression analysis was used to identify the modules associated with nonresponse to IFX therapy for RA, and enrichment analysis was conducted on module genes. Least absolute shrink and selection operator (LASSO) regression was used to develop a gene signature for predicting the therapeutic effect of IFX in RA, and the area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive value of the signature. Correlation analysis and single-sample gene set enrichment analysis (ssGSEA) were used to explore the potential role of the hub genes. Experimental validation was conducted in synovial tissue and RA fibroblast-like synoviocytes (RA-FLSs). RESULTS: A total of 46 common genes were obtained among the two datasets. The yellow-green module was identified as the key module associated with nonresponse to IFX therapy for RA. We identified a 25-gene signature in GSE78068, and the AUC for the signature was 0.831 in the internal validation set and 0.924 in the GSE58795 dataset(external validation set). Derlin-1 (DERL1) was identified as the hub gene and demonstrated to be involved in the immune response and autophagy regulation. DERL1 expression was increased in RA synovial tissue compared with OA synovial tissue, and DERL1-siRNA partially inhibited autophagosome formation in RA-FLSs. CONCLUSION: The 25-gene signature may have potential predictive value for the therapeutic effect of IFX in RA at the beginning of IFX treatment, and autophagy may be involved in nonresponse to IFX treatment. In particular, DERL1 may be associated with the regulation of autophagy.
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spelling pubmed-87622142022-01-18 Derlin-1, as a Potential Early Predictive Biomarker for Nonresponse to Infliximab Treatment in Rheumatoid Arthritis, Is Related to Autophagy Cai, Yongsong Xu, Ke Aihaiti, Yirixiati Li, Zhijin Yuan, Qiling Xu, Jing Zheng, Haishi Yang, Mingyi Wang, Bo Yang, Yanni Yang, Yin Xu, Peng Front Immunol Immunology BACKGROUND: The goal of this study was to identify potential predictive biomarkers for the therapeutic effect of infliximab (IFX) in Rheumatoid arthritis (RA) and explore the potential molecular mechanism of nonresponse to IFX treatment to achieve individualized treatment of RA. METHODS: Differential gene expression between IFX responders and nonresponders in the GSE58795 and GSE78068 datasets was identified. Coexpression analysis was used to identify the modules associated with nonresponse to IFX therapy for RA, and enrichment analysis was conducted on module genes. Least absolute shrink and selection operator (LASSO) regression was used to develop a gene signature for predicting the therapeutic effect of IFX in RA, and the area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive value of the signature. Correlation analysis and single-sample gene set enrichment analysis (ssGSEA) were used to explore the potential role of the hub genes. Experimental validation was conducted in synovial tissue and RA fibroblast-like synoviocytes (RA-FLSs). RESULTS: A total of 46 common genes were obtained among the two datasets. The yellow-green module was identified as the key module associated with nonresponse to IFX therapy for RA. We identified a 25-gene signature in GSE78068, and the AUC for the signature was 0.831 in the internal validation set and 0.924 in the GSE58795 dataset(external validation set). Derlin-1 (DERL1) was identified as the hub gene and demonstrated to be involved in the immune response and autophagy regulation. DERL1 expression was increased in RA synovial tissue compared with OA synovial tissue, and DERL1-siRNA partially inhibited autophagosome formation in RA-FLSs. CONCLUSION: The 25-gene signature may have potential predictive value for the therapeutic effect of IFX in RA at the beginning of IFX treatment, and autophagy may be involved in nonresponse to IFX treatment. In particular, DERL1 may be associated with the regulation of autophagy. Frontiers Media S.A. 2022-01-03 /pmc/articles/PMC8762214/ /pubmed/35046954 http://dx.doi.org/10.3389/fimmu.2021.795912 Text en Copyright © 2022 Cai, Xu, Aihaiti, Li, Yuan, Xu, Zheng, Yang, Wang, Yang, Yang and Xu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Cai, Yongsong
Xu, Ke
Aihaiti, Yirixiati
Li, Zhijin
Yuan, Qiling
Xu, Jing
Zheng, Haishi
Yang, Mingyi
Wang, Bo
Yang, Yanni
Yang, Yin
Xu, Peng
Derlin-1, as a Potential Early Predictive Biomarker for Nonresponse to Infliximab Treatment in Rheumatoid Arthritis, Is Related to Autophagy
title Derlin-1, as a Potential Early Predictive Biomarker for Nonresponse to Infliximab Treatment in Rheumatoid Arthritis, Is Related to Autophagy
title_full Derlin-1, as a Potential Early Predictive Biomarker for Nonresponse to Infliximab Treatment in Rheumatoid Arthritis, Is Related to Autophagy
title_fullStr Derlin-1, as a Potential Early Predictive Biomarker for Nonresponse to Infliximab Treatment in Rheumatoid Arthritis, Is Related to Autophagy
title_full_unstemmed Derlin-1, as a Potential Early Predictive Biomarker for Nonresponse to Infliximab Treatment in Rheumatoid Arthritis, Is Related to Autophagy
title_short Derlin-1, as a Potential Early Predictive Biomarker for Nonresponse to Infliximab Treatment in Rheumatoid Arthritis, Is Related to Autophagy
title_sort derlin-1, as a potential early predictive biomarker for nonresponse to infliximab treatment in rheumatoid arthritis, is related to autophagy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762214/
https://www.ncbi.nlm.nih.gov/pubmed/35046954
http://dx.doi.org/10.3389/fimmu.2021.795912
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