title: Simultaneous analysis of the expression of 14 genes with individual prognostic value in myelodysplastic syndrome patients at diagnosis: WT1 detection in peripheral blood adversely affects survival.
abstract: Several studies have evaluated the prognostic value of the individual expression of certain genes in patients with myelodysplastic syndromes (MDS). However, none of them includes their simultaneous analysis by quantitative polymerase chain reaction (PCR). We evaluated relative expression levels of 14 molecular markers in 193 peripheral blood samples from untreated MDS patients using real-time PCR. Detectable WT1 expression levels, low TET2, and low IER3 gene expression were the only markers showing in univariate analysis a poor prognostic value for all treatment-free (TFS), progression-free (PFS), and overall survival (OS). In multivariate analysis, molecular parameters associated with a shorter TFS were: WT1 detection (p = 0.014), low TET2 (p = 0.002), and low IER3 expression (p = 0.025). WT1 detection (p = 0.006) and low TET2 (p = 0.006) expression were associated with a shorter PFS when multivariate analysis was carried out by including only molecular markers. Molecular values with an independent value in OS were: WT1 detection (p = 0.003), high EVI1 expression (p = 0.001), and undetectatable p15-CDKN2B (p = 0.037). WT1 expressers were associated with adverse clinical-biological features, high IPSS and WPSS scoring, and unfavorable molecular expression profile. In summary, detectable WT1 expression levels, and low TET2 and low IER3 expression in peripheral blood showed a strong association with adverse prognosis in MDS patients at diagnosis. However, WT1 was the only molecular marker displaying an independent prognostic value in both OS and TFS.
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, Salamanca 37007, Spain. cmsantamaria@usal.es
authors.forename: Carlos
authors.initials: C
authors.lastname: Santamaría
authors.forename: Fernando
authors.initials: F
authors.lastname: Ramos
authors.forename: Noemi
authors.initials: N
authors.lastname: Puig
authors.forename: Eva
authors.initials: E
authors.lastname: Barragán
authors.forename: Raquel
authors.initials: R
authors.lastname: de Paz
authors.forename: Carme
authors.initials: C
authors.lastname: Pedro
authors.forename: Andrés
authors.initials: A
authors.lastname: Insunza
authors.forename: Mar
authors.initials: M
authors.lastname: Tormo
authors.forename: Consuelo
authors.initials: C
authors.lastname: Del Cañizo
authors.forename: María
authors.initials: M
authors.lastname: Diez-Campelo
authors.forename: Blanca
authors.initials: B
authors.lastname: Xicoy
authors.forename: Eduardo
authors.initials: E
authors.lastname: Salido
authors.forename: Javier
authors.initials: J
authors.lastname: Sánchez del Real
authors.forename: Montserrat
authors.initials: M
authors.lastname: Hernández
authors.forename: Carmen
authors.initials: C
authors.lastname: Chillón
authors.forename: Guillermo F
authors.initials: GF
authors.lastname: Sanz
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Marcos
authors.initials: M
authors.lastname: González
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D001773:Blood Cells / Q000378:metabolism*; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D049308:Dioxygenases; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D025721:WT1 Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C099815:IER3 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D025721:WT1 Proteins; D049308:Dioxygenases; C541081:TET2 protein, human