Pipinikas Christodoulos P, Carter Nicholas D, Corbishley Catherine M, Fenske Christiane D
Division of Clinical Developmental Sciences, Medical Genetics, St George's University of London, Cranmer Terrace, London, UK.
Biomarkers. 2008 Nov;13(7):680-91. doi: 10.1080/13547500802591992.
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.
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.
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.
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.
多项临床研究表明，癌症的侵袭性生长和转移性疾病发生率取决于缺氧程度，而缺氧由缺氧诱导因子1α（HIF-1α）介导。为了确定其作为前列腺癌（CaP）诊断标志物的潜在作用，我们检测了被诊断为不同阶段前列腺疾病患者血液样本中的HIF-1α mRNA水平。
通过定量逆转录聚合酶链反应（qRT-PCR）检测HIF-1α mRNA水平，并将其与准确的临床病理数据相关联。将定量数据与血清前列腺特异性抗原（PSA）测量结果进行比较，以确定CaP诊断准确性的差异。
与无恶性证据（NEOM）和良性前列腺增生（BPH）患者（两组患者共35例）相比，局限性CaP患者（LocCaP；n = 63；p < 0.0001）的HIF-1α mRNA水平显著上调。受试者操作特征（ROC）曲线分析表明，HIF-1α对NEOM/BPH诊断的特异性为88.6%。对LocCaP的敏感性为74.6%，总体诊断效率为79.6%。PSA水平为4.0 ng ml(-1)时，NEOM诊断的特异性为28.6%，LocCap诊断的敏感性为65.1%，与HIF-1α测量结果相比，总体诊断效率降低，为52.0%。转移性CaP患者（MetCaP；n = 27）的HIF-1α水平与NEOM/BPH组相似。
HIF-1α在CaP发展早期上调，随后在晚期转移阶段下调。本研究表明，与血清PSA测量相比，使用HIF-1α qRT-PCR诊断早期疾病的准确性更高。因此，HIF-1α可能是一种有用的辅助手段，与相对qRT-PCR中使用的其他诊断标志物和当前诊断技术（包括血清PSA和PSA速度）一起，以尽量减少仅由血清PSA水平升高指示的不必要活检。
