title: An integrated proteomic approach to identifying circulating biomarkers in high-risk neuroblastoma and their potential in relapse monitoring.
abstract: OBJECTIVE
  Despite intensive treatment regimens, overall survival for high-risk neuroblastoma (HRNB) is still poor. This is in part due to an inability to cure the disease once a patient has reached clinical relapse. Identifying plasma biomarkers of active disease may provide a way of relapse monitoring in HRNB.
  
  
  METHODS
  In this study, we developed an integrated proteomic approach to identify plasma biomarkers for HRNB.
  
  
  RESULTS
  We identified seven candidate biomarkers (SAA, APOA1, IL-6, EGF, MDC, sCD40L and Eotaxin) for HRNB. These biomarkers were then used to create a multivariate classifier of HRNB, which showed a specificity of 90% (95% confidence interval (CI), 73%, 98%), and a sensitivity of 81% (95%CI, 54%, 96%) for classifying HRNB in a training set. When evaluated on independent test samples, the classifier exhibited 86% accuracy (95% CI, 42%, 100%) of identifying diagnostic samples, and 86% accuracy (95% CI, 70%, 100%) of detecting post-diagnosis longitudinal samples that having active disease.
  
  
  CONCLUSIONS
  Further validation of these biomarkers may improve patients' outcomes by developing a simple blood test for the detection of relapse prior to the development of clinically evident disease. Understanding the role of these biomarkers in immune surveillance of neuroblastoma may also provide a new direction of therapeutic strategies.
authors.affiliation: Texas Children's Cancer Center, Houston, TX, USA.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Egler
authors.forename: Yiting
authors.initials: Y
authors.lastname: Li
authors.forename: Tu Anh T
authors.initials: TA
authors.lastname: Dang
authors.forename: Tricia L
authors.initials: TL
authors.lastname: Peters
authors.forename: Eastwood
authors.initials: E
authors.lastname: Leung
authors.forename: Shixia
authors.initials: S
authors.lastname: Huang
authors.forename: Heidi V
authors.initials: HV
authors.lastname: Russell
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Tsz-Kwong
authors.initials: TK
authors.lastname: Man
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000175:diagnosis* / Q000378:metabolism / Q000517:prevention & control; D040901:Proteomics / Q000379:methods*; D012008:Recurrence; D012307:Risk Factors; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D016207:Cytokines