Frontiers in Molecular Biosciences (Nov 2023)
Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritis
- 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
Affiliations
- Jianan Zhao
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Jianan Zhao
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Jianan Zhao
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Kai Wei
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Kai Wei
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Kai Wei
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Yiming Shi
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Yiming Shi
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Yiming Shi
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Ping Jiang
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Ping Jiang
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Ping Jiang
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Lingxia Xu
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Lingxia Xu
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Lingxia Xu
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Cen Chang
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Cen Chang
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Cen Chang
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Linshuai Xu
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Linshuai Xu
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Linshuai Xu
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Yixin Zheng
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Yixin Zheng
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Yixin Zheng
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Yu Shan
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Yu Shan
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Yu Shan
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Jia Liu
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Jia Liu
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Jia Liu
- Arthritis Institute of Integrated Traditional and Western Medicine, Shanghai Chinese Medicine Research Institute, Shanghai, China
- Li Li
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Li Li
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Li Li
- Arthritis Institute of Integrated Traditional and Western Medicine, Shanghai Chinese Medicine Research Institute, Shanghai, China
- Shicheng Guo
- Computation and Informatics in Biology and Medicine, University of Wisconsin-Madison, Madison, WIUnited States
- Shicheng Guo
- Department of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
- Steven J. Schrodi
- Computation and Informatics in Biology and Medicine, University of Wisconsin-Madison, Madison, WIUnited States
- Steven J. Schrodi
- Department of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
- Rongsheng Wang
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Rongsheng Wang
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Rongsheng Wang
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Dongyi He
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Dongyi He
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Dongyi He
- Arthritis Institute of Integrated Traditional and Western Medicine, Shanghai Chinese Medicine Research Institute, Shanghai, China
- Dongyi He
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- DOI
- https://doi.org/10.3389/fmolb.2023.1202371
- Journal volume & issue
-
Vol. 10
Abstract
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.
Keywords
- rheumatoid arthritis
- anoikis-related molecular clusters
- anoikis
- cell death
- immunological characterization