Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritis

Objective: To investigate the potential association between Anoikis-related genes, which are responsible for preventing abnormal cellular proliferation, and rheumatoid arthritis (RA).Methods: Datasets GSE89408, GSE198520, and GSE97165 were obtained from the GEO with 282 RA patients and 28 healthy co...

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Main Authors: Jianan Zhao, Kai Wei, Yiming Shi, Ping Jiang, Lingxia Xu, Cen Chang, Linshuai Xu, Yixin Zheng, Yu Shan, Jia Liu, Li Li, Shicheng Guo, Steven J. Schrodi, Rongsheng Wang, Dongyi He
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-11-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2023.1202371/full
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author Jianan Zhao
Jianan Zhao
Jianan Zhao
Kai Wei
Kai Wei
Kai Wei
Yiming Shi
Yiming Shi
Yiming Shi
Ping Jiang
Ping Jiang
Ping Jiang
Lingxia Xu
Lingxia Xu
Lingxia Xu
Cen Chang
Cen Chang
Cen Chang
Linshuai Xu
Linshuai Xu
Linshuai Xu
Yixin Zheng
Yixin Zheng
Yixin Zheng
Yu Shan
Yu Shan
Yu Shan
Jia Liu
Jia Liu
Jia Liu
Li Li
Li Li
Li Li
Shicheng Guo
Shicheng Guo
Steven J. Schrodi
Steven J. Schrodi
Rongsheng Wang
Rongsheng Wang
Rongsheng Wang
Dongyi He
Dongyi He
Dongyi He
Dongyi He
author_facet Jianan Zhao
Jianan Zhao
Jianan Zhao
Kai Wei
Kai Wei
Kai Wei
Yiming Shi
Yiming Shi
Yiming Shi
Ping Jiang
Ping Jiang
Ping Jiang
Lingxia Xu
Lingxia Xu
Lingxia Xu
Cen Chang
Cen Chang
Cen Chang
Linshuai Xu
Linshuai Xu
Linshuai Xu
Yixin Zheng
Yixin Zheng
Yixin Zheng
Yu Shan
Yu Shan
Yu Shan
Jia Liu
Jia Liu
Jia Liu
Li Li
Li Li
Li Li
Shicheng Guo
Shicheng Guo
Steven J. Schrodi
Steven J. Schrodi
Rongsheng Wang
Rongsheng Wang
Rongsheng Wang
Dongyi He
Dongyi He
Dongyi He
Dongyi He
author_sort Jianan Zhao
collection DOAJ
description Objective: To investigate the potential association between Anoikis-related genes, which are responsible for preventing abnormal cellular proliferation, and rheumatoid arthritis (RA).Methods: Datasets GSE89408, GSE198520, and GSE97165 were obtained from the GEO with 282 RA patients and 28 healthy controls. We performed differential analysis of all genes and HLA genes. We performed a protein-protein interaction network analysis and identified hub genes based on STRING and cytoscape. Consistent clustering was performed with subgrouping of the disease. SsGSEA were used to calculate immune cell infiltration. Spearman’s correlation analysis was employed to identify correlations. Enrichment scores of the GO and KEGG were calculated with the ssGSEA algorithm. The WGCNA and the DGIdb database were used to mine hub genes’ interactions with drugs.Results: There were 26 differentially expressed Anoikis-related genes (FDR = 0.05, log2FC = 1) and HLA genes exhibited differential expression (P < 0.05) between the disease and control groups. Protein-protein interaction was observed among differentially expressed genes, and the correlation between PIM2 and RAC2 was found to be the highest; There were significant differences in the degree of immune cell infiltration between most of the immune cell types in the disease group and normal controls (P < 0.05). Anoikis-related genes were highly correlated with HLA genes. Based on the expression of Anoikis-related genes, RA patients were divided into two disease subtypes (cluster1 and cluster2). There were 59 differentially expressed Anoikis-related genes found, which exhibited significant differences in functional enrichment, immune cell infiltration degree, and HLA gene expression (P < 0.05). Cluster2 had significantly higher levels in all aspects than cluster1 did. The co-expression network analysis showed that cluster1 had 51 hub differentially expressed genes and cluster2 had 72 hub differentially expressed genes. Among them, three hub genes of cluster1 were interconnected with 187 drugs, and five hub genes of cluster2 were interconnected with 57 drugs.Conclusion: Our study identified a link between Anoikis-related genes and RA, and two distinct subtypes of RA were determined based on Anoikis-related gene expression. Notably, cluster2 may represent a more severe state of RA.
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spelling doaj.art-81442de10ea8486985e5fb5e045128ab2023-11-18T10:07:03ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-11-011010.3389/fmolb.2023.12023711202371Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritisJianan Zhao0Jianan Zhao1Jianan Zhao2Kai Wei3Kai Wei4Kai Wei5Yiming Shi6Yiming Shi7Yiming Shi8Ping Jiang9Ping Jiang10Ping Jiang11Lingxia Xu12Lingxia Xu13Lingxia Xu14Cen Chang15Cen Chang16Cen Chang17Linshuai Xu18Linshuai Xu19Linshuai Xu20Yixin Zheng21Yixin Zheng22Yixin Zheng23Yu Shan24Yu Shan25Yu Shan26Jia Liu27Jia Liu28Jia Liu29Li Li30Li Li31Li Li32Shicheng Guo33Shicheng Guo34Steven J. Schrodi35Steven J. Schrodi36Rongsheng Wang37Rongsheng Wang38Rongsheng Wang39Dongyi He40Dongyi He41Dongyi He42Dongyi He43Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaArthritis Institute of Integrated Traditional and Western Medicine, Shanghai Chinese Medicine Research Institute, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaArthritis Institute of Integrated Traditional and Western Medicine, Shanghai Chinese Medicine Research Institute, Shanghai, ChinaComputation and Informatics in Biology and Medicine, University of Wisconsin-Madison, Madison, WIUnited StatesDepartment of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesComputation and Informatics in Biology and Medicine, University of Wisconsin-Madison, Madison, WIUnited StatesDepartment of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaArthritis Institute of Integrated Traditional and Western Medicine, Shanghai Chinese Medicine Research Institute, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaObjective: To investigate the potential association between Anoikis-related genes, which are responsible for preventing abnormal cellular proliferation, and rheumatoid arthritis (RA).Methods: Datasets GSE89408, GSE198520, and GSE97165 were obtained from the GEO with 282 RA patients and 28 healthy controls. We performed differential analysis of all genes and HLA genes. We performed a protein-protein interaction network analysis and identified hub genes based on STRING and cytoscape. Consistent clustering was performed with subgrouping of the disease. SsGSEA were used to calculate immune cell infiltration. Spearman’s correlation analysis was employed to identify correlations. Enrichment scores of the GO and KEGG were calculated with the ssGSEA algorithm. The WGCNA and the DGIdb database were used to mine hub genes’ interactions with drugs.Results: There were 26 differentially expressed Anoikis-related genes (FDR = 0.05, log2FC = 1) and HLA genes exhibited differential expression (P < 0.05) between the disease and control groups. Protein-protein interaction was observed among differentially expressed genes, and the correlation between PIM2 and RAC2 was found to be the highest; There were significant differences in the degree of immune cell infiltration between most of the immune cell types in the disease group and normal controls (P < 0.05). Anoikis-related genes were highly correlated with HLA genes. Based on the expression of Anoikis-related genes, RA patients were divided into two disease subtypes (cluster1 and cluster2). There were 59 differentially expressed Anoikis-related genes found, which exhibited significant differences in functional enrichment, immune cell infiltration degree, and HLA gene expression (P < 0.05). Cluster2 had significantly higher levels in all aspects than cluster1 did. The co-expression network analysis showed that cluster1 had 51 hub differentially expressed genes and cluster2 had 72 hub differentially expressed genes. Among them, three hub genes of cluster1 were interconnected with 187 drugs, and five hub genes of cluster2 were interconnected with 57 drugs.Conclusion: Our study identified a link between Anoikis-related genes and RA, and two distinct subtypes of RA were determined based on Anoikis-related gene expression. Notably, cluster2 may represent a more severe state of RA.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1202371/fullrheumatoid arthritisanoikis-related molecular clustersanoikiscell deathimmunological characterization
spellingShingle Jianan Zhao
Jianan Zhao
Jianan Zhao
Kai Wei
Kai Wei
Kai Wei
Yiming Shi
Yiming Shi
Yiming Shi
Ping Jiang
Ping Jiang
Ping Jiang
Lingxia Xu
Lingxia Xu
Lingxia Xu
Cen Chang
Cen Chang
Cen Chang
Linshuai Xu
Linshuai Xu
Linshuai Xu
Yixin Zheng
Yixin Zheng
Yixin Zheng
Yu Shan
Yu Shan
Yu Shan
Jia Liu
Jia Liu
Jia Liu
Li Li
Li Li
Li Li
Shicheng Guo
Shicheng Guo
Steven J. Schrodi
Steven J. Schrodi
Rongsheng Wang
Rongsheng Wang
Rongsheng Wang
Dongyi He
Dongyi He
Dongyi He
Dongyi He
Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritis
Frontiers in Molecular Biosciences
rheumatoid arthritis
anoikis-related molecular clusters
anoikis
cell death
immunological characterization
title Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritis
title_full Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritis
title_fullStr Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritis
title_full_unstemmed Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritis
title_short Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritis
title_sort identification of immunological characterization and anoikis related molecular clusters in rheumatoid arthritis
topic rheumatoid arthritis
anoikis-related molecular clusters
anoikis
cell death
immunological characterization
url https://www.frontiersin.org/articles/10.3389/fmolb.2023.1202371/full
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