title: A molecular and computational diagnostic approach identifies FOXP3, ICOS, CD52 and CASP1 as the most informative biomarkers in acute graft-versus-host disease.
abstract: BACKGROUND
  Acute graft-versus-host disease is a severe complication of allogeneic stem cell transplantation in which the functional immune cells of the donor recognize the recipient as foreign and mount an immunological attack. There is an urgent need for better diagnostic instruments for the assessment of acute graft-versus-host disease. In the present study, a novel bioinformatics framework was used to identify gene expression patterns associated with acute graft-versushost disease in patients undergoing allogeneic hematopoietic stem cell transplantation.
  
  
  METHODS
  Peripheral blood cells were collected prospectively from patients who did develop acute graftversus-host disease (YES) and from those who did not (NO). Gene expression profiling was performed using a panel of 47 candidate genes potentially involved in alloreactive responses. The entire population of YES/NO acute graft-versus-host disease patients formed the experimental validation set. Personalized modeling based on a gene selection technique was applied to identify the most significant mRNA transcripts, which were then used to profile individual data samples for training and testing the classification/prediction framework.
  
  
  RESULTS
  A leave-one-out cross-validation procedure was performed to investigate the robustness of the classification framework producing the following results: 100% on the training dataset and 97% on the testing dataset. According to our integrated methodology, transcripts for FOXP3, ICOS, CD52 and CASP1, genes involved in immune alloreactive responses and participating in immune cell interactions, were identified as the most informative biomarkers in allogeneic stem cell transplant recipients experiencing acute graft-versus-host disease.
  
  
  CONCLUSIONS
  This study demonstrates that the integrated methodology proposed is useful for the selection of valid gene targets for the diagnosis of acute graft-versus-host disease, producing satisfactory accuracy over independent clinical features of the allogeneic transplanted population.
authors.affiliation: Transplant Regional Center of Stem Cells and Cellular Therapy, A. Neri, Reggio Calabria, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Cuzzola
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fiasché
authors.forename: Pasquale
authors.initials: P
authors.lastname: Iacopino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Messina
authors.forename: Massimo
authors.initials: M
authors.lastname: Martino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Console
authors.forename: Roberta
authors.initials: R
authors.lastname: Fedele
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Recchia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Irrera
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers; D000074301:CD52 Antigen; D020170:Caspase 1 / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D057285:Precision Medicine; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015415:Biomarkers; D000074301:CD52 Antigen; C000613862:CD52 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006023:Glycoproteins; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D020170:Caspase 1