title: KIAA1199 as a potential diagnostic biomarker of rheumatoid arthritis related to angiogenesis.
abstract: BACKGROUND
  Our previous proteomic study on fibroblast-like synoviocytes (FLSs) derived from the synovial tissues found that the expression of KIAA1199 was higher in rheumatoid arthritis (RA) patients than in healthy controls. The aim of this study was to examine the biological function of KIAA1199 and evaluate its clinical diagnosis value in RA.
  
  
  METHODS
  The over-expression of KIAA1199 was verified by quantitative real-time polymerase chain reaction (qPCR), Immunohistochemistry, Immunofluorescence and enzyme linked immunosorbent assay (ELISA) in inactive and active RA patients and healthy controls. The effect of KIAA1199 expression on FLSs proliferation, angiogenesis and related pathway were analyzed by MTT, cell migration, tube formation, chorioallantoic membrane (CAM) assay, qPCR and western-blotting after KIAA1199 knockdown and over-expression.
  
  
  RESULTS
  The verification results show the up-regulation of KIAA1199 in RA patients at mRNA and protein level as compared to that in healthy controls. ELISA and receiver operator characteristic (ROC) analysis shows that KIAA1199 concentration in serum, synovial fluid and synovial tissues could be used as dependable biomarkers for the diagnosis of active RA, provided an area under roc curve (AUC) of 0.83, 0.92 and 0.92. Sensitivity and specificity, which were determined by cut-off points, reached 72% 84% and 80% in sensitivity and 80%, 93.3%, 93.3% in specificity, respectively. Moreover, KIAA1199 also enhance the proliferation and angiogenesis of synovial membrane, and KIAA1199/ PLXNB3/ SEMA5A/CTGF axis may be a newly found pathway enhancing cell proliferation and angiogenesis.
  
  
  CONCLUSIONS
  KIAA1199 may be a potential diagnostic biomarker of RA related to angiogenesis.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China. cyrillyoung@163.com.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China. 347004915@qq.com.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Qiu
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China. 738877136@qq.com.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China. 398560338@qq.com.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China. 475634534@qq.com.
authors.forename: Zhonghao
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China. 1729844779@qq.com.
authors.forename: Renshan
authors.initials: R
authors.lastname: Ge
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China. 512586826@qq.com.
authors.forename: Hai
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Rheumatology, Jiamusi Central Hospital, Jiamusi, China. wangjiangmin1968@126.com.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China. wz_wjg@163.com.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Wang
mesh_terms: D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000175:diagnosis*; D015415:Biomarkers / Q000032:analysis*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006821:Hyaluronoglucosaminidase; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011506:Proteins; C491433:CEMIP protein, human; D006821:Hyaluronoglucosaminidase