University of Leipzig, Department of Urology, Leipzig, Germany.
PLoS One. 2013 Jun 24;8(6):e67514. doi: 10.1371/journal.pone.0067514. Print 2013.
Extensive prostate specific antigen screening for prostate cancer generates a high number of unnecessary biopsies and over-treatment due to insufficient differentiation between indolent and aggressive tumours. We hypothesized that seminal plasma is a robust source of novel prostate cancer (PCa) biomarkers with the potential to improve primary diagnosis of and to distinguish advanced from indolent disease.
METHODOLOGY/PRINCIPAL FINDINGS: In an open-label case/control study 125 patients (70 PCa, 21 benign prostate hyperplasia, 25 chronic prostatitis, 9 healthy controls) were enrolled in 3 centres. Biomarker panels a) for PCa diagnosis (comparison of PCa patients versus benign controls) and b) for advanced disease (comparison of patients with post surgery Gleason score <7 versus Gleason score >7) were sought. Independent cohorts were used for proteomic biomarker discovery and testing the performance of the identified biomarker profiles. Seminal plasma was profiled using capillary electrophoresis mass spectrometry. Pre-analytical stability and analytical precision of the proteome analysis were determined. Support vector machine learning was used for classification. Stepwise application of two biomarker signatures with 21 and 5 biomarkers provided 83% sensitivity and 67% specificity for PCa detection in a test set of samples. A panel of 11 biomarkers for advanced disease discriminated between patients with Gleason score 7 and organ-confined (<pT3a) or advanced (≥pT3a) disease with 80% sensitivity and 82% specificity in a preliminary validation setting. Seminal profiles showed excellent pre-analytical stability. Eight biomarkers were identified as fragments of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase, prostatic acid phosphatase, stabilin-2, GTPase IMAP family member 6, semenogelin-1 and -2. Restricted sample size was the major limitation of the study.
CONCLUSIONS/SIGNIFICANCE: Seminal plasma represents a robust source of potential peptide makers for primary PCa diagnosis. Our findings warrant further prospective validation to confirm the diagnostic potential of identified seminal biomarker candidates.
广泛的前列腺特异性抗原（PSA）筛查前列腺癌会导致大量不必要的活检和过度治疗，因为其无法区分惰性和侵袭性肿瘤。我们假设，精浆是一种强大的新型前列腺癌（PCa）生物标志物来源，具有改善PCa 初步诊断和区分晚期与惰性疾病的潜力。
方法/主要发现：在一项开放标签病例对照研究中，纳入了来自 3 个中心的 125 名患者（70 名 PCa 患者，21 名良性前列腺增生患者，25 名慢性前列腺炎患者，9 名健康对照者）。研究寻求用于 a）PCa 诊断（PCa 患者与良性对照组比较）和 b）晚期疾病（术后 Gleason 评分<7 与>Gleason 评分>7 患者比较）的生物标志物面板。使用毛细管电泳质谱法对精浆进行蛋白质组生物标志物分析。确定了蛋白质组分析的预分析稳定性和分析精密度。使用支持向量机学习进行分类。在测试样本集中，使用具有 21 和 5 个生物标志物的两个生物标志物特征的逐步应用，可实现 83%的 PCa 检测敏感性和 67%的特异性。用于晚期疾病的 11 个生物标志物面板在初步验证中，可在 Gleason 评分 7 与器官受限（<pT3a）或晚期（≥pT3a）疾病的患者之间进行区分，其敏感性为 80%，特异性为 82%。精浆谱显示出极好的预分析稳定性。确定了 8 个生物标志物是 N-乙酰乳糖胺β-1,3-N-乙酰氨基葡萄糖基转移酶、前列腺酸性磷酸酶、稳定素-2、GTP 酶 IMAP 家族成员 6、精液蛋白 1 和 -2 的片段。样本量有限是本研究的主要局限性。
结论/意义：精浆是潜在肽标志物的强大来源，可用于 PCa 的初步诊断。我们的研究结果需要进一步的前瞻性验证，以确认所鉴定的精浆生物标志物候选物的诊断潜力。
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