OBJECTIVES: Several clinical studies have indicated that the rates of invasive growth and metastatic disease in cancer depend on the degree of hypoxia, which is mediated by hypoxia-inducible factor 1 alpha (HIF-1alpha). To determine its potential role as a marker for prostate cancer (CaP) diagnosis, HIF-1alpha mRNA levels were measured in blood samples of patients diagnosed with different stages of prostatic disease. METHODS: HIF-1alpha mRNA levels were measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and correlated with accurate clinicopathological data. Quantitative data were compared with serum prostate-specific antigen (PSA) measurements to determine variations in the accuracy of the CaP diagnosis. RESULTS: HIF-1alpha mRNA levels were significantly upregulated in patients with localized CaP (LocCaP; n=63; p<0.0001), compared with patients with no evidence of malignancy (NEOM) and benign prostatic hyperplasia (BPH) (n=35 for both patient groups combined). Receiver operator characteristic (ROC) curve analysis demonstrated that HIF-1alpha specificity for the NEOM/BPH diagnosis was 88.6%. Sensitivity for LocCaP was 74.6% with an overall diagnostic efficiency of 79.6%. Specificity of the NEOM diagnosis at PSA levels of 4.0 ng ml(-1) was 28.6% and sensitivity of the LocCap diagnosis was 65.1%, demonstrating a reduced overall diagnostic efficiency, compared with that given by HIF-1alpha measurements, of 52.0%. Levels of HIF-1alpha in patients with metastatic CaP (MetCaP; n=27)) were similar to those in the NEOM/BPH group. CONCLUSIONS: HIF-1alpha is upregulated early in CaP development with subsequent downregulation at later metastatic stages. This study demonstrates increased accuracy of early-stage disease diagnosis using HIF-1alpha qRT-PCR compared with serum PSA measurements. HIF-1alpha may therefore be a useful adjunct, together with other diagnostic markers used in relative qRT-PCR and current diagnostic techniques (including serum PSA and PSA velocity) to minimize unnecessary biopsies indicated by elevated serum PSA levels alone.
OBJECTIVES: Several clinical studies have indicated that the rates of invasive growth and metastatic disease in cancer depend on the degree of hypoxia, which is mediated by hypoxia-inducible factor 1 alpha (HIF-1alpha). To determine its potential role as a marker for prostate cancer (CaP) diagnosis, HIF-1alpha mRNA levels were measured in blood samples of patients diagnosed with different stages of prostatic disease. METHODS:HIF-1alpha mRNA levels were measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and correlated with accurate clinicopathological data. Quantitative data were compared with serum prostate-specific antigen (PSA) measurements to determine variations in the accuracy of the CaP diagnosis. RESULTS:HIF-1alpha mRNA levels were significantly upregulated in patients with localized CaP (LocCaP; n=63; p<0.0001), compared with patients with no evidence of malignancy (NEOM) and benign prostatic hyperplasia (BPH) (n=35 for both patient groups combined). Receiver operator characteristic (ROC) curve analysis demonstrated that HIF-1alpha specificity for the NEOM/BPH diagnosis was 88.6%. Sensitivity for LocCaP was 74.6% with an overall diagnostic efficiency of 79.6%. Specificity of the NEOM diagnosis at PSA levels of 4.0 ng ml(-1) was 28.6% and sensitivity of the LocCap diagnosis was 65.1%, demonstrating a reduced overall diagnostic efficiency, compared with that given by HIF-1alpha measurements, of 52.0%. Levels of HIF-1alpha in patients with metastatic CaP (MetCaP; n=27)) were similar to those in the NEOM/BPH group. CONCLUSIONS:HIF-1alpha is upregulated early in CaP development with subsequent downregulation at later metastatic stages. This study demonstrates increased accuracy of early-stage disease diagnosis using HIF-1alpha qRT-PCR compared with serum PSA measurements. HIF-1alpha may therefore be a useful adjunct, together with other diagnostic markers used in relative qRT-PCR and current diagnostic techniques (including serum PSA and PSA velocity) to minimize unnecessary biopsies indicated by elevated serum PSA levels alone.
Authors: Weranja K B Ranasinghe; Graham S Baldwin; Arthur Shulkes; Damien Bolton; Oneel Patel Journal: Nat Rev Urol Date: 2014-07-01 Impact factor: 14.432
Authors: Narasimhan Kothandaraman; Vladimir B Bajic; Pang N K Brendan; Chan Y Huak; Peh B Keow; Khalil Razvi; Manuel Salto-Tellez; Mahesh Choolani Journal: BMC Cancer Date: 2010-02-24 Impact factor: 4.430
Authors: Weranja K B Ranasinghe; Lin Xiao; Suzana Kovac; Mike Chang; Carine Michiels; Damien Bolton; Arthur Shulkes; Graham S Baldwin; Oneel Patel Journal: PLoS One Date: 2013-01-16 Impact factor: 3.240