新型非侵入性生物标志物，可区分前列腺增生和前列腺癌。
Novel non-invasive biomarkers that distinguish between benign prostate hyperplasia and prostate cancer.
机构信息
Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
出版信息
BMC Cancer. 2015 Apr 11;15:259. doi: 10.1186/s12885-015-1284-z.
BACKGROUND
The objective of this study was to discover and to validate novel noninvasive biomarkers that distinguish between benign prostate hyperplasia (BPH) and localized prostate cancer (PCa), thereby helping to solve the diagnostic dilemma confronting clinicians who treat these patients.
METHODS
Quantitative iTRAQ LC/LC/MS/MS analysis was used to identify proteins that are differentially expressed in the urine of men with BPH compared with those who have localized PCa. These proteins were validated in 173 urine samples from patients diagnosed with BPH (N = 83) and PCa (N = 90). Multivariate logistic regression analysis was used to identify the predictive biomarkers.
RESULTS
Three proteins, β2M, PGA3, and MUC3 were identified by iTRAQ and validated by immunoblot analyses. Univariate analysis demonstrated significant elevations in urinary β2M (P < 0.001), PGA3 (P = 0.006), and MUC3 (P = 0.018) levels found in the urine of PCa patients. Multivariate logistic regression analysis revealed AUC values ranging from 0.618 for MUC3 (P = 0.009), 0.625 for PGA3 (P < 0.008), and 0.668 for β2M (P < 0.001). The combination of all three demonstrated an AUC of 0.710 (95% CI: 0.631 - 0.788, P < 0.001); diagnostic accuracy improved even more when these data were combined with PSA categories (AUC = 0.812, (95% CI: 0.740 - 0.885, P < 0.001).
CONCLUSIONS
Urinary β2M, PGA3, and MUC3, when analyzed alone or when multiplexed with clinically defined categories of PSA, may be clinically useful in noninvasively resolving the dilemma of effectively discriminating between BPH and localized PCa.
背景
本研究的目的是发现并验证新的非侵入性生物标志物，以区分良性前列腺增生（BPH）和局限性前列腺癌（PCa），从而帮助解决治疗这些患者的临床医生面临的诊断难题。
方法
采用定量 iTRAQ LC/LC/MS/MS 分析方法，鉴定出与患有局限性 PCa 的男性相比，在 BPH 男性尿液中差异表达的蛋白质。在 173 份诊断为 BPH（n=83）和 PCa（n=90）患者的尿液样本中对这些蛋白质进行了验证。采用多元逻辑回归分析来识别预测生物标志物。
结果
通过 iTRAQ 鉴定出 3 种蛋白质，β2M、PGA3 和 MUC3，并通过免疫印迹分析进行了验证。单因素分析表明，PCa 患者尿液中β2M（P < 0.001）、PGA3（P = 0.006）和 MUC3（P = 0.018）水平显著升高。多元逻辑回归分析显示，MUC3 的 AUC 值范围为 0.618（P = 0.009）、PGA3 的 AUC 值范围为 0.625（P < 0.008）、β2M 的 AUC 值范围为 0.668（P < 0.001）。三者联合的 AUC 值为 0.710（95%CI：0.631-0.788，P < 0.001）；当将这些数据与 PSA 类别相结合时，诊断准确性进一步提高（AUC=0.812，95%CI：0.740-0.885，P < 0.001）。
结论
当单独分析或与临床定义的 PSA 类别联合分析时，尿液中的β2M、PGA3 和 MUC3 可能在非侵入性地有效区分 BPH 和局限性 PCa 方面具有临床应用价值。
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