Integrative analysis for identification of shared markers from various functional cells/tissues for rheumatoid arthritis.
Rheumatoid arthritis (RA) is a systemic autoimmune disease. So far, it is unclear whether there exist common RA-related genes shared in different tissues/cells. In this study, we conducted an integrative analysis on multiple datasets to identify potential shared genes that are significant in multiple tissues/cells for RA. Seven microarray gene expression datasets representing various RA-related tissues/cells were downloaded from the Gene Expression Omnibus (GEO). Statistical analyses, testing both marginal and joint effects, were conducted to identify significant genes shared in various samples. Followed-up analyses were conducted on functional annotation clustering analysis, protein-protein interaction (PPI) analysis, gene-based association analysis, and ELISA validation analysis in in-house samples. We identified 18 shared significant genes, which were mainly involved in the immune response and chemokine signaling pathway. Among the 18 genes, eight genes (PPBP, PF4, HLA-F, S100A8, RNASEH2A, P2RY6, JAG2, and PCBP1) interact with known RA genes. Two genes (HLA-F and PCBP1) are significant in gene-based association analysis (P = 1.03E-31, P = 1.30E-2, respectively). Additionally, PCBP1 also showed differential protein expression levels in in-house case-control plasma samples (P = 2.60E-2). This study represented the first effort to identify shared RA markers from different functional cells or tissues. The results suggested that one of the shared genes, i.e., PCBP1, is a promising biomarker for RA.
Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China.
Wei
W
Xia
Department of Rheumatology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, People's Republic of China.
Jian
J
Wu
Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China.
Fei-Yan
FY
Deng
Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China.
Long-Fei
LF
Wu
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China.
Yong-Hong
YH
Zhang
Department of Rheumatology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, People's Republic of China. gyf3636@sina.com.cn.
Yu-Fan
YF
Guo
Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China. leisf@suda.edu.cn.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China. leisf@suda.edu.cn.
Shu-Feng
SF
Lei
D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis*; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D060066:Protein Interaction Maps
D015415:Biomarkers
Integrative analysis; Multi-dataset analysis; Rheumatoid arthritis; Shared genetic marker