用于准确检测良性前列腺增生患者中前列腺癌的潜在尿液蛋白生物标志物候选物。
Potential Urinary Protein Biomarker Candidates for the Accurate Detection of Prostate Cancer among Benign Prostatic Hyperplasia Patients.
机构信息
1. Centre for Biotechnology, Brock University, St. Catharines, ON, L2S 3A1, Canada.
2. Department of Biochemistry, Faculty of Science, Alexandria University, Egypt.
出版信息
J Cancer. 2014 Jan 5;5(2):103-14. doi: 10.7150/jca.6890. eCollection 2014.
Globally, Prostate cancer (PCa) is the most frequently occurring non-cutaneous cancer, and is the second highest cause of cancer mortality in men. Serum prostate specific antigen (PSA) has been the standard in PCa screening since its approval by the American Food & Drug Administration (FDA) in 1994. Currently, PSA is used as an indicator for PCa - patients with a serum PSA level above 4ng/mL will often undergo prostate biopsy to confirm cancer. Unfortunately fewer than ~30% of these men will biopsy positive for cancer, meaning that the majority of men undergo invasive biopsy with little benefit. Despite PSA's notoriously poor specificity (33%), there is still a significant lack of credible alternatives. Therefore an ideal biomarker that can specifically detect PCa at an early stage is urgently required. The aim of this study was to investigate the potential of using deregulation of urinary proteins in order to detect Prostate Cancer (PCa) among Benign Prostatic Hyperplasia (BPH). To identify the protein signatures specific for PCa, protein expression profiling of 8 PCa patients, 12 BPH patients and 10 healthy males was carried out using LC-MS/MS. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This approach revealed that significant the down-regulation of Fibronectin and TP53INP2 was a characteristic event among PCa patients. Fibronectin mRNA down-regulation, was identified as offering improved specificity (50%) over PSA, albeit with a slightly lower although still acceptable sensitivity (75%) for detecting PCa. As for TP53INP2 on the other hand, its down-regulation was moderately sensitive (75%), identifying many patients with PCa, but was entirely non-specific (7%), designating many of the benign samples as malignant and being unable to accurately identify more than one negative.
在全球范围内，前列腺癌（PCa）是最常见的非皮肤癌，也是男性癌症死亡率第二高的原因。血清前列腺特异性抗原（PSA）自 1994 年获得美国食品和药物管理局（FDA）批准以来，一直是 PCa 筛查的标准。目前，PSA 被用作 PCa 的指标-血清 PSA 水平高于 4ng/mL 的患者通常会进行前列腺活检以确认癌症。不幸的是，这些男性中只有~30%的人会活检出癌症，这意味着大多数男性进行了侵入性活检，但获益甚微。尽管 PSA 的特异性（33%）很差，但仍然缺乏可靠的替代品。因此，迫切需要一种能够在早期特异性检测 PCa 的理想生物标志物。本研究旨在探讨利用尿液蛋白失调来检测前列腺增生（BPH）中的前列腺癌（PCa）的潜力。为了鉴定 PCa 特异性的蛋白标志物，使用 LC-MS/MS 对 8 名 PCa 患者、12 名 BPH 患者和 10 名健康男性进行了蛋白表达谱分析。随后使用定量实时 PCR 验证了所有患者尿液中存在的蛋白的相对表达水平。这一方法揭示了 Fibronectin 和 TP53INP2 的下调是 PCa 患者的一个特征性事件。Fibronectin mRNA 的下调被确定为提供了比 PSA 更高的特异性（50%），尽管其检测 PCa 的敏感性（75%）略低，但仍然可以接受。另一方面，TP53INP2 的下调具有中等敏感性（75%），可识别许多患有 PCa 的患者，但完全没有特异性（7%），将许多良性样本标记为恶性，并且无法准确识别一个以上的阴性样本。
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