PMID- 30483789 OWN - NLM STAT- MEDLINE DCOM- 20190528 LR - 20211011 IS - 1791-3004 (Electronic) IS - 1791-2997 (Print) IS - 1791-2997 (Linking) VI - 19 IP - 1 DP - 2019 Jan TI - Identification of potential biomarkers for differential diagnosis between rheumatoid arthritis and osteoarthritis via integrative genome‑wide gene expression profiling analysis. PG - 30-40 LID - 10.3892/mmr.2018.9677 [doi] AB - The present study aimed to identify potential novel biomarkers in synovial tissue obtained from patients with Rheumatoid Arthritis (RA) and Osteoarthritis (OA) for differential diagnosis. The genome‑wide expression profiling datasets of synovial tissues from RA and OA cohorts, including GSE55235, GSE55457 and GSE55584 datasets, were retrieved and used to identify differentially expressed genes (DEGs; P<0.05; false discovery rate <0.05 and Fold Change >2) between RA and OA using R software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs were performed to determine molecular and biochemical pathways associated with the identified DEGs, and a protein‑protein interaction (PPI) network of the DEGs was constructed using Cytoscape software. Significant modules in the PPI network and candidate driver genes were screened using the Molecular Complex Detection Algorithm. Potential biomarkers were evaluated by receiver operating characteristic and logistic regression analyses. Large numbers of DEGs were detected, including 273, 205 and 179 DEGs in the GSE55235, GSE55457 and GSE55584 datasets, respectively. Among them, 80 DEGs exhibited identical expression trends in all the three datasets, including 49 upregulated and 31 downregulated genes in patients with RA. DEGs in patients suffering from RA compared with patients suffering from OA were predominantly associated with the primary immunodeficiency pathway, including interleukin 7 receptor (IL7R) and signal transducer activator of transcription 1 (STAT1). The sensitivity of IL7R + STAT1 to differentiate RA from OA was 93.94% with a specificity of 80.77%. The results generated from analyses of the GSE36700 dataset were closely associated with results generated from analyses of GSE55235, GSE55457 and GSE55584 datasets, which further verified the reliability of the aforementioned results. The results of the present study suggested that increased expression of IL7R and STAT1 in synovial tissue as well as in the primary immunodeficiency may be associated with RA occurrence. These identified novel biomarkers may be used to predict disease occurrence and clinically differentiate RA from OA. FAU - Zhang, Rongqiang AU - Zhang R AD - School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of The National Health and Family Planning Commission, Xi'an, Shaanxi 710061, P.R. China. FAU - Yang, Xiaoli AU - Yang X AD - School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of The National Health and Family Planning Commission, Xi'an, Shaanxi 710061, P.R. China. FAU - Wang, Jing AU - Wang J AD - School of Public Health, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, P.R. China. FAU - Han, Lixin AU - Han L AD - School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of The National Health and Family Planning Commission, Xi'an, Shaanxi 710061, P.R. China. FAU - Yang, Aimin AU - Yang A AD - School of Public Health, Brown University, Providence, RI 02906, USA. FAU - Zhang, Jie AU - Zhang J AD - School of Public Health, Brown University, Providence, RI 02906, USA. FAU - Zhang, Dandan AU - Zhang D AD - School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of The National Health and Family Planning Commission, Xi'an, Shaanxi 710061, P.R. China. FAU - Li, Baorong AU - Li B AD - School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of The National Health and Family Planning Commission, Xi'an, Shaanxi 710061, P.R. China. FAU - Li, Zhaofang AU - Li Z AD - School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of The National Health and Family Planning Commission, Xi'an, Shaanxi 710061, P.R. China. FAU - Xiong, Yongmin AU - Xiong Y AD - School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of The National Health and Family Planning Commission, Xi'an, Shaanxi 710061, P.R. China. LA - eng PT - Journal Article DEP - 20181120 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Biomarkers) RN - 0 (Receptors, Interleukin-7) RN - 0 (STAT1 Transcription Factor) SB - IM MH - Arthritis, Rheumatoid/*genetics MH - Biomarkers/*metabolism MH - Databases, Genetic MH - Diagnosis, Differential MH - Down-Regulation/genetics MH - Gene Expression Profiling/methods MH - Gene Ontology MH - Gene Regulatory Networks/genetics MH - Genome-Wide Association Study/methods MH - Humans MH - Osteoarthritis/*genetics MH - Protein Interaction Maps/genetics MH - Receptors, Interleukin-7/genetics MH - Reproducibility of Results MH - STAT1 Transcription Factor/genetics MH - Software MH - Synovial Membrane/metabolism MH - Transcriptome/*genetics MH - Up-Regulation/genetics PMC - PMC6297798 OTO - NOTNLM OT - rheumatoid arthritis OT - osteoarthritis OT - pathway OT - protein-protein interaction OT - sensitivity OT - specificity EDAT- 2018/11/30 06:00 MHDA- 2019/05/29 06:00 PMCR- 2018/11/20 CRDT- 2018/11/29 06:00 PHST- 2018/05/31 00:00 [received] PHST- 2018/09/24 00:00 [accepted] PHST- 2018/11/30 06:00 [pubmed] PHST- 2019/05/29 06:00 [medline] PHST- 2018/11/29 06:00 [entrez] PHST- 2018/11/20 00:00 [pmc-release] AID - mmr-19-01-0030 [pii] AID - 10.3892/mmr.2018.9677 [doi] PST - ppublish SO - Mol Med Rep. 2019 Jan;19(1):30-40. doi: 10.3892/mmr.2018.9677. Epub 2018 Nov 20.