Τίτλος:
mRNA overexpression of the hypoxia inducible factor 1 alpha subunit gene (HIF1A): An independent predictor of poor overall survival in chronic lymphocytic leukemia
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The hypoxia inducible factor 1 (HIF1) is a heterodimeric transcription factor that ultimately regulates cellular responses to changes in oxygen tension. In this study, we examined the potential diagnostic and prognostic potential of the mRNA expression of HIF1 regulatory α-subunit (HIF1A) in chronic lymphocytic leukemia (CLL). For this purpose, total RNA was isolated from peripheral blood mononuclear cells collected from 88 CLL patients and 33 non-leukemic blood donors, and poly(A)-RNA was reversely transcribed. HIF1A mRNA levels were quantified using real-time PCR. Kaplan-Meier survival analysis showed that high HIF1A mRNA expression predicts inferior overall survival for CLL patients (p = 0.001). Bootstrap univariate Cox regression analysis confirmed that HIF1A mRNA overexpression is a significant unfavorable prognosticator in CLL (hazard ratio = 3.75, bias-corrected and accelerated 95% confidence interval = 1.43–24.36, bootstrap p < 0.001), independent of other established prognostic factors, including CD38 expression, the mutational status of the immunoglobulin heavy chain variable region (IGHV), and the clinical stage (Binet or Rai stage) or risk group (p < 0.001 in all cases). Interestingly, HIF1A mRNA positivity retains its unfavorable prognostic value in distinct subgroups of patients, stratified according to established prognostic factors. Thus, HIF1A mRNA overexpression can be regarded as a promising, independent molecular biomarker of unfavorable prognosis in CLL. © 2016 Elsevier Ltd
Συγγραφείς:
Kontos, C.K.
Papageorgiou, S.G.
Diamantopoulos, M.A.
Scorilas, A.
Bazani, E.
Vasilatou, D.
Gkontopoulos, K.
Glezou, E.
Stavroulaki, G.
Dimitriadis, G.
Pappa, V.
Περιοδικό:
Leukemia Research
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
CD38 antigen; hypoxia inducible factor 1alpha; immunoglobulin heavy chain; messenger RNA; HIF1A protein, human; hypoxia inducible factor 1alpha; messenger RNA; tumor marker, accuracy; adult; Article; blood sampling; cancer prognosis; cancer survival; chronic lymphatic leukemia; controlled study; disease marker; female; gene overexpression; human; human cell; leukemia cell; leukocyte count; lymphocyte count; major clinical study; male; overall survival; peripheral blood mononuclear cell; priority journal; protein expression; real time polymerase chain reaction; receiver operating characteristic; sequence analysis; survival rate; blood; case control study; genetics; Leukemia, Lymphocytic, Chronic, B-Cell; mortality; prognosis, Biomarkers, Tumor; Case-Control Studies; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Leukemia, Lymphocytic, Chronic, B-Cell; Prognosis; RNA, Messenger; Survival Rate
DOI:
10.1016/j.leukres.2016.11.014
