CLP1 is a Prognosis-Related Biomarker and Correlates With Immune Infiltrates in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, heterogeneous autoimmune disease with a high disability rate that seriously affects society and individuals. However, there is a lack of effective and reliable diagnostic markers and therapeutic targets. In this study, we identified diagnostic markers of RA ba...

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Main Authors: Zhenyu Zhao, Shaojie He, Sheng Tang, Xiaofeng Lai, Jie Ren, XinCheng Yu, Jinhua Lin, Mohan Wang, Mariya M. El Akkawi, Shan Zeng, Dingsheng Zha
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.827215/full
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author Zhenyu Zhao
Shaojie He
Sheng Tang
Xiaofeng Lai
Jie Ren
XinCheng Yu
Jinhua Lin
Mohan Wang
Mariya M. El Akkawi
Shan Zeng
Dingsheng Zha
author_facet Zhenyu Zhao
Shaojie He
Sheng Tang
Xiaofeng Lai
Jie Ren
XinCheng Yu
Jinhua Lin
Mohan Wang
Mariya M. El Akkawi
Shan Zeng
Dingsheng Zha
author_sort Zhenyu Zhao
collection DOAJ
description Rheumatoid arthritis (RA) is a chronic, heterogeneous autoimmune disease with a high disability rate that seriously affects society and individuals. However, there is a lack of effective and reliable diagnostic markers and therapeutic targets. In this study, we identified diagnostic markers of RA based on RNA modification and explored its role as well as degree of immune cell infiltration. We used the gene expression profile data of three synovial tissues (GSE55235, GSE55457, GSE77298) from the Gene Expression Omnibus (GEO) database and the gene of 5 RNA modification genes (including m6A, m1A, m5C, APA, A-1), combined with cluster analysis, identified four RNA modifiers closely related to RA (YTHDC1, LRPPRC, NOP2, and CLP1) and five immune cells namely T cell CD8, CD4 memory resting, T cells regulatory (Tregs) Macrophages M0, and Neutrophils. Based on the LASSO regression algorithm, hub genes and immune cell prediction models were established respectively in RA and a nomogram based on the immune cell model was built. Around 4 key RNA modification regulator genes, miRNA-mRNA, mRNA-TF networks have been established, and GSEA-GO, KEGG-GSEA enrichment analysis has been carried out. Finally, CLP1 was established as an effective RA diagnostic marker, and was highly positively correlated with T cells follicular helper (Tfh) infiltration. On the other hand, highly negatively correlated with the expression of mast cells. In short, CLP1 may play a non-negligible role in the onset and development of RA by altering immune cell infiltration, and it is predicted to represent a novel target for RA clinical diagnosis and therapy.
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spelling doaj.art-e68efc1b3ca44d1bb71afb6c48e6ed572022-12-22T00:33:02ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-06-011310.3389/fphar.2022.827215827215CLP1 is a Prognosis-Related Biomarker and Correlates With Immune Infiltrates in Rheumatoid ArthritisZhenyu Zhao0Shaojie He1Sheng Tang2Xiaofeng Lai3Jie Ren4XinCheng Yu5Jinhua Lin6Mohan Wang7Mariya M. El Akkawi8Shan Zeng9Dingsheng Zha10Department of Orthopaedics, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Orthopaedics, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Orthopaedics, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Orthopaedics, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Rheumatology, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Orthopaedics, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Orthopaedics, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaSchool of Basic Medicine and Public Health, Jinan University, Guangzhou, ChinaDepartment of Plastic and Reconstructive Surgery, Zhujiang Hospital of Southern Medical University, Guangzhou, ChinaDepartment of Rheumatology, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Orthopaedics, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaRheumatoid arthritis (RA) is a chronic, heterogeneous autoimmune disease with a high disability rate that seriously affects society and individuals. However, there is a lack of effective and reliable diagnostic markers and therapeutic targets. In this study, we identified diagnostic markers of RA based on RNA modification and explored its role as well as degree of immune cell infiltration. We used the gene expression profile data of three synovial tissues (GSE55235, GSE55457, GSE77298) from the Gene Expression Omnibus (GEO) database and the gene of 5 RNA modification genes (including m6A, m1A, m5C, APA, A-1), combined with cluster analysis, identified four RNA modifiers closely related to RA (YTHDC1, LRPPRC, NOP2, and CLP1) and five immune cells namely T cell CD8, CD4 memory resting, T cells regulatory (Tregs) Macrophages M0, and Neutrophils. Based on the LASSO regression algorithm, hub genes and immune cell prediction models were established respectively in RA and a nomogram based on the immune cell model was built. Around 4 key RNA modification regulator genes, miRNA-mRNA, mRNA-TF networks have been established, and GSEA-GO, KEGG-GSEA enrichment analysis has been carried out. Finally, CLP1 was established as an effective RA diagnostic marker, and was highly positively correlated with T cells follicular helper (Tfh) infiltration. On the other hand, highly negatively correlated with the expression of mast cells. In short, CLP1 may play a non-negligible role in the onset and development of RA by altering immune cell infiltration, and it is predicted to represent a novel target for RA clinical diagnosis and therapy.https://www.frontiersin.org/articles/10.3389/fphar.2022.827215/fullrheumatoid arthritisRNA modificationdiagnostic biomarkersgene expression profile dataCLP1
spellingShingle Zhenyu Zhao
Shaojie He
Sheng Tang
Xiaofeng Lai
Jie Ren
XinCheng Yu
Jinhua Lin
Mohan Wang
Mariya M. El Akkawi
Shan Zeng
Dingsheng Zha
CLP1 is a Prognosis-Related Biomarker and Correlates With Immune Infiltrates in Rheumatoid Arthritis
Frontiers in Pharmacology
rheumatoid arthritis
RNA modification
diagnostic biomarkers
gene expression profile data
CLP1
title CLP1 is a Prognosis-Related Biomarker and Correlates With Immune Infiltrates in Rheumatoid Arthritis
title_full CLP1 is a Prognosis-Related Biomarker and Correlates With Immune Infiltrates in Rheumatoid Arthritis
title_fullStr CLP1 is a Prognosis-Related Biomarker and Correlates With Immune Infiltrates in Rheumatoid Arthritis
title_full_unstemmed CLP1 is a Prognosis-Related Biomarker and Correlates With Immune Infiltrates in Rheumatoid Arthritis
title_short CLP1 is a Prognosis-Related Biomarker and Correlates With Immune Infiltrates in Rheumatoid Arthritis
title_sort clp1 is a prognosis related biomarker and correlates with immune infiltrates in rheumatoid arthritis
topic rheumatoid arthritis
RNA modification
diagnostic biomarkers
gene expression profile data
CLP1
url https://www.frontiersin.org/articles/10.3389/fphar.2022.827215/full
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