title: Proteomic profiling of pretreatment serum from HIV-infected patients identifies candidate markers predictive of lymphoma development.
abstract: HIV-infected individuals have an increased risk of developing lymphoma. We sought to identify markers predictive of lymphoma development by comparing protein expression patterns in serum obtained at the time of HIV diagnosis from patients who later developed malignant lymphoma or benign lymphadenopathy, with samples from patients with no subsequent history of neoplasia.
  
  
  
  All patients were identified retrospectively from the Danish HIV cohort.
  
  
  
  Serum samples (N = 21), obtained at time of HIV diagnosis, were subjected to high-resolution two-dimensional gel electrophoresis. Differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry. A tissue microarray, containing diagnostic HIV-lymphoma tissue samples (N = 40), was used to investigate immunohistochemical expression of markers in tumoural lesions.
  
  
  
  Fourteen differentially expressed protein spots were detected. Using principal components analysis, spots containing immunoglobulin J chain, apolipoprotein A-I, procollagen C-endopeptidase enhancer-1 and complement C4-A were associated with lymphoma development (P < 0.0001). Serum amyloid A-2 was increased almost 10-fold in patients with subsequent lymphoma compared with patients without subsequent lymphoma. In the tissue microarray, amyloid A was widely expressed, and high expression showed a tendency towards inferior outcome (log-rank 0.073).
  
  
  
  We identified several differentially expressed protein spots present already at the time of HIV diagnosis. Analysis of biological differences correlating to lymphoma development at this early stage of a possible malignant transformation may lead to the identification of predictive markers. Further investigation of the potential clinical application of differentially expressed proteins as risk stratification markers for monitoring HIV-positive individuals is warranted.
authors.affiliation: aDepartment of Haematology, Aarhus University HospitalbDepartment of Biomedicine, Aarhus UniversitycInstitute of Pathology, Aarhus University Hospital, AarhusdDepartment of PathologyeDepartment of Infectious Diseases, Odense University Hospital, OdensefDepartment of Infectious Diseases, Aalborg University Hospital, AalborggThe Danish HIV Cohort, Department of Infectious Diseases, Copenhagen University Hospital, CopenhagenhDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.*Maja Ølholm Vase and Maja Ludvigsen shared first authorships.†Francesco d'Amore and Bent Honoré shared last authorships.
authors.forename: Maja Ølholm
authors.initials: MØ
authors.lastname: Vase
authors.forename: Maja
authors.initials: M
authors.lastname: Ludvigsen
authors.forename: Knud
authors.initials: K
authors.lastname: Bendix
authors.forename: Stephen
authors.initials: S
authors.lastname: Hamilton-Dutoit
authors.forename: Michael Boe
authors.initials: MB
authors.lastname: Mller
authors.forename: Court
authors.initials: C
authors.lastname: Pedersen
authors.forename: Gitte
authors.initials: G
authors.lastname: Pedersen
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.forename: Carsten Schade
authors.initials: CS
authors.lastname: Larsen
authors.forename: Francesco
authors.initials: F
authors.lastname: d'Amore
authors.forename: Bent
authors.initials: B
authors.lastname: Honoré
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis*; D002853:Chromatography, Liquid; D003718:Denmark; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008223:Lymphoma / Q000473:pathology*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D040901:Proteomics; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry*; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins