Novel splice variants of prostate-specific antigen and applications in diagnosis of prostate cancer

ObjectivesWe aimed to identify novel splice variants of prostate-specific antigen/or human kallikrein 3 (PSA/KLK3), the most widely used serum biomarker for case-finding, screening and monitoring of prostate cancer.Design and methodsThe full-length sequences of splice variants were assembled as contigs from human ESTs that displayed homology to the cDNA sequence encoding PSA. Expression of variants in clinical samples was analyzed by semi-quantitative RT-PCR.ResultsEST database mining led to the identification of seven previously unidentified splice variants encoding PSA-like proteins that are predicted to contain epitope sequences recognized by PSA-specific antibodies, therefore, expression of these isoforms may affect the amount of total PSA measured by established immunoassays. Analysis of the differential expression profile of isoform PSA-SV5 in patients with benign prostate hyperplasia and prostate cancer showed that it is specifically expressed in prostate cancers.ConclusionsA novel splice variant of PSA was identified, PSA-SV5, that may be exploited in clinical diagnosis to distinguish prostate cancer from benign prostate hyperplasia.