Yulan Chen1, Ruobing Liao1, Yuxin Yao1, Qiao Wang1, Lingyu Fu2,3. 1. Department of Clinical Epidemiology and Evidence-Based Medicine, The First Affiliated Hospital, China Medical University, No.155, Nan Jing Bei Street, Shenyang, Liaoning Province, China. 2. Department of Clinical Epidemiology and Evidence-Based Medicine, The First Affiliated Hospital, China Medical University, No.155, Nan Jing Bei Street, Shenyang, Liaoning Province, China. fulingyucmu@sina.com. 3. Department of Medical Record Management Center, The First Affiliated Hospital, China Medical University, Shenyang, China. fulingyucmu@sina.com.
Abstract
OBJECTIVES: This study was designed to identify the potential diagnostic biomarkers of rheumatoid arthritis (RA) and to explore the potential pathological relevance of immune cell infiltration in this disease. METHODS: Three previously published datasets containing gene expression data from 35 RA patients and 29 controls (GSE55235, GSE55457, and GSE12021) were downloaded from the GEO database, after which a weighted correlation network analysis (WGCNA) approach was utilized to clarify differentially abundant genes. Candidate biomarkers of RA were then identified via the use of a LASSO regression model and support vector machine recursive feature elimination (SVM-RFE) analyses. Data were validated based upon the area under the receiver operating characteristic curve (AUC) values, with hub genes being identified as those with an AUC > 85% and a P value < 0.05. Lastly, the CIBERSORT algorithm was used to assess immune cell infiltration of RA tissues, and correlations between immune cell infiltration and disease-related diagnostic biomarkers were assessed. RESULTS: The green-yellow module containing 87 genes was found to be highly correlated with RA positivity. FADD, CXCL2, and CXCL8 were identified as potential RA diagnostic biomarkers (AUC > 0.85), and these results were validated using the GSE77298 dataset. Immune cell infiltration analyses revealed the expression of hub genes to be correlated with mast cells, monocytes, activated NK cells, CD8 T cells, resting dendritic cells, and plasma cells. CONCLUSION: These data indicate that FADD, CXCL2, and CXCL8 are valuable diagnostic biomarkers of RA, offering new insight that can guide future studies of RA incidence and progression.
OBJECTIVES: This study was designed to identify the potential diagnostic biomarkers of rheumatoid arthritis (RA) and to explore the potential pathological relevance of immune cell infiltration in this disease. METHODS: Three previously published datasets containing gene expression data from 35 RA patients and 29 controls (GSE55235, GSE55457, and GSE12021) were downloaded from the GEO database, after which a weighted correlation network analysis (WGCNA) approach was utilized to clarify differentially abundant genes. Candidate biomarkers of RA were then identified via the use of a LASSO regression model and support vector machine recursive feature elimination (SVM-RFE) analyses. Data were validated based upon the area under the receiver operating characteristic curve (AUC) values, with hub genes being identified as those with an AUC > 85% and a P value < 0.05. Lastly, the CIBERSORT algorithm was used to assess immune cell infiltration of RA tissues, and correlations between immune cell infiltration and disease-related diagnostic biomarkers were assessed. RESULTS: The green-yellow module containing 87 genes was found to be highly correlated with RA positivity. FADD, CXCL2, and CXCL8 were identified as potential RA diagnostic biomarkers (AUC > 0.85), and these results were validated using the GSE77298 dataset. Immune cell infiltration analyses revealed the expression of hub genes to be correlated with mast cells, monocytes, activated NK cells, CD8 T cells, resting dendritic cells, and plasma cells. CONCLUSION: These data indicate that FADD, CXCL2, and CXCL8 are valuable diagnostic biomarkers of RA, offering new insight that can guide future studies of RA incidence and progression.
Authors: Aaron M Newman; Chih Long Liu; Michael R Green; Andrew J Gentles; Weiguo Feng; Yue Xu; Chuong D Hoang; Maximilian Diehn; Ash A Alizadeh Journal: Nat Methods Date: 2015-03-30 Impact factor: 28.547