title: Opportunities and challenges of proteomics in pediatric patients: circulating biomarkers after hematopoietic stem cell transplantation as a successful example.
abstract: Biomarkers have the potential to improve diagnosis and prognosis, facilitate-targeted treatment, and reduce health care costs. Thus, there is great hope that biomarkers will be integrated in all clinical decisions in the near future. A decade ago, the biomarker field was launched with great enthusiasm because MS revealed that blood contains a rich library of candidate biomarkers. However, biomarker research has not yet delivered on its promise due to several limitations: (i) improper sample handling and tracking as well as limited sample availability in the pediatric population, (ii) omission of appropriate controls in original study designs, (iii) lability and low abundance of interesting biomarkers in blood, and (iv) the inability to mechanistically tie biomarker presence to disease biology. These limitations as well as successful strategies to overcome them are discussed in this review. Several advances in biomarker discovery and validation have been made in hematopoietic stem cell transplantation, the current most effective tumor immunotherapy, and these could serve as examples for other conditions. This review provides fresh optimism that biomarkers clinically relevant in pediatrics are closer to being realized based on: (i) a uniform protocol for low-volume blood collection and preservation, (ii) inclusion of well-controlled independent cohorts, (iii) novel technologies and instrumentation with low analytical sensitivity, and (iv) integrated animal models for exploring potential biomarkers and targeted therapies.
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Paczesny
authors.forename: Christine
authors.initials: C
authors.lastname: Duncan
authors.forename: David
authors.initials: D
authors.lastname: Jacobsohn
authors.forename: Robert
authors.initials: R
authors.lastname: Krance
authors.forename: Kathryn
authors.initials: K
authors.lastname: Leung
authors.forename: Paul
authors.initials: P
authors.lastname: Carpenter
authors.forename: Catherine
authors.initials: C
authors.lastname: Bollard
authors.forename: Jamie
authors.initials: J
authors.lastname: Renbarger
authors.forename: Kenneth
authors.initials: K
authors.lastname: Cooke
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D002648:Child; D006086:Graft vs Host Disease / Q000097:blood / Q000175:diagnosis; D006402:Hematologic Diseases / Q000097:blood / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D020543:Proteome
keywords: Biomarkers; Graft-versus-Host Disease; Hematopoietic stem cell transplantation; Pediatrics; Risk stratification