Proteomics-based signature for human benign prostate hyperplasia and prostate adenocarcinoma

Abstract

Abstract. Prostate adenocarcinoma often presents at a late stage, due to a lack of early clinical symptoms and lack of accurate objective markers. This study aimed to identify and validate proteomics-based biomarkers useful for prostate cancer diagnosis and to establish a marker-panel for prostate cancer and benign prostate hyperplasia (BPH). Global protein expression patterns in fresh tissue specimens from 8 patients with prostate carcinoma and 16 with BPH were analyzed by two-dimensional gel electrophoresis. Differentially expressed proteins were identified by MALDI-TOF mass spectrometry. We compared our results with those of published studies and defined a set of common biomarkers. We identified 22 differentially expressed proteins between BPH and prostate carcinomas. The up-regulated proteins in cancer compared to BPH included protein disulfide-isomerase, 14-3-3-protein, Enoyl CoA-hydrase, prohibitin and B-tubulin β-2. Keratin-II, desmin, HSP71, ATP-synthase-β-chain and creatine kinase-β-chain were down-regulated. Survey of the literature showed that 15 of our 22 identified proteins have been previously reported to differ in their expression levels between BPH and prostate cancer by other laboratories. The expression patterns of these biomarkers could successfully cluster BPH and adenocarcinomas as well as prostate cancer of low and high Gleason scores. This study validates protein-biomarkers that can be useful for accurate diagnosis and prognostic monitoring of prostate adenocarcinoma. Despite varied prevalence of the disease between different ethnic populations (i.e., high in Sweden, low in Saudi Arabia); the biomarkers indicate that BPH and prostate cancers are biologically 'homogeneous' in their protein expression patterns across wide geographical regions. IntroductionProstate cancer accounts for approximately 25% of all newly diagnosed cancers and is the second leading cause of cancer deaths among the male population in America (1,2). While the prevalence of prostate cancer is relatively low in Saudi Arabia, it is the most commonly diagnosed cancer in men in Sweden (3). Even though the molecular variations in prostate carcinomas across wide geographical regions have not been extensively studied, the disease is relatively more common among AfroAmericans and often present with advanced stage disease compared to what is observed in American white men (4,5).An improvement and widespread availability in the measurement of PSA, such as PSA density, PSA volume and adjusted age-specific PSA ranges has resulted in early disease diagnosis in the Western world (6). However, many malignant cases still elude early detection and patients often present with metastasis at time of diagnosis (7,8) especially in the less developed world. Patients with occult metastases usually do not benefit from radical prostatectomy or radiotherapy and often respond less favorably to hormonal treatment (5,9). Prostate cancer is biologically heterogeneous with unpredictable aggressive behavior and currently the molecular events underlyin...

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