富含半胱氨酸的分泌蛋白3和β-微精蛋白与根治性前列腺切除术后结局的关联
Association of cysteine-rich secretory protein 3 and beta-microseminoprotein with outcome after radical prostatectomy.
作者信息
Bjartell Anders S, Al-Ahmadie Hikmat, Serio Angel M, Eastham James A, Eggener Scott E, Fine Samson W, Udby Lene, Gerald William L, Vickers Andrew J, Lilja Hans, Reuter Victor E, Scardino Peter T
机构信息
Departments of Surgery (Urology), Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
出版信息
Clin Cancer Res. 2007 Jul 15;13(14):4130-8. doi: 10.1158/1078-0432.CCR-06-3031.
PURPOSE
It has been suggested that cysteine-rich secretory protein 3 (CRISP-3) and beta-microseminoprotein (MSP) are associated with outcome in prostate cancer. We investigated whether these markers are related to biochemical recurrence and whether addition of the markers improves prediction of recurring disease.
EXPERIMENTAL DESIGN
Tissue microarrays of radical prostatectomy specimens were analyzed for CRISP-3 and MSP by immunohistochemistry. Associations between marker positivity and postprostatectomy biochemical recurrence [prostate-specific antigen (PSA) >0.2 ng/mL with a confirmatory level] were evaluated by univariate and multivariable Cox proportional hazards regression. Multivariable analyses controlled for preoperative PSA and pathologic stage and grade.
RESULTS
Among 945 patients, 224 had recurrence. Median follow-up for survivors was 6.0 years. Patients positive for CRISP-3 had smaller recurrence-free probabilities, whereas MSP-positive patients had larger recurrence-free probabilities. On univariate analysis, the hazard ratio for patients positive versus negative for CRISP-3 was 1.53 (P=0.010) and for MSP was 0.63 (P=0.004). On multivariable analysis, both CRISP-3 (P=0.007) and MSP (P=0.002) were associated with recurrence. The hazard ratio among CRISP-3-positive/MSP-negative patients compared with CRISP-3-negative/MSP-positive patients was 2.38. Adding CRISP-3 to a base model that included PSA and pathologic stage and grade did not enhance the prediction of recurrence, but adding MSP increased the concordance index minimally from 0.778 to 0.781.
CONCLUSION
We report evidence that CRISP-3 and MSP are independent predictors of recurrence after radical prostatectomy for localized prostate cancer. However, addition of the markers does not importantly improve the performance of existing predictive models. Further research should aim to elucidate the functions of CRISP-3 and MSP in prostate cancer cells.
目的
有人提出富含半胱氨酸的分泌蛋白3（CRISP-3）和β-微精蛋白（MSP）与前列腺癌的预后相关。我们研究了这些标志物是否与生化复发相关，以及添加这些标志物是否能改善对复发性疾病的预测。
实验设计
通过免疫组织化学分析前列腺癌根治术标本的组织微阵列中的CRISP-3和MSP。通过单变量和多变量Cox比例风险回归评估标志物阳性与前列腺切除术后生化复发[前列腺特异性抗原（PSA）>0.2 ng/mL并达到确认水平]之间的关联。多变量分析对术前PSA、病理分期和分级进行了控制。
结果
在945例患者中，224例出现复发。幸存者的中位随访时间为6.0年。CRISP-3阳性的患者无复发概率较小，而MSP阳性的患者无复发概率较大。单变量分析中，CRISP-3阳性患者与阴性患者相比的风险比为1.53（P=0.010），MSP为0.63（P=0.004）。多变量分析中，CRISP-3（P=0.007）和MSP（P=0.002）均与复发相关。CRISP-3阳性/MSP阴性患者与CRISP-3阴性/MSP阳性患者相比的风险比为2.38。在包含PSA、病理分期和分级的基础模型中添加CRISP-3并没有增强对复发的预测，但添加MSP使一致性指数从0.778略有增加至0.781。
结论
我们报告的证据表明，CRISP-3和MSP是局限性前列腺癌根治术后复发的独立预测因子。然而，添加这些标志物并没有显著改善现有预测模型的性能。进一步的研究应旨在阐明CRISP-3和MSP在前列腺癌细胞中的功能。
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