NOXA and PUMA expression add to clinical markers in predicting biochemical recurrence of prostate cancer patients in a survival tree model
NOXA and PUMA expression add to clinical markers in predicting biochemical recurrence of prostate cancer patients in a survival tree model
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DOI：
10.1158/1078-0432.ccr-07-1224
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发表时间：
2007-12-01
影响因子：
11.5
通讯作者：
Saad, Fred
中科院分区：
文献类型：
--
作者：
Diallo, Jean-Simon;Aldejmah, Abdulhadi;Saad, Fred
目的：为了评估前列腺组织中促凋亡NOXA和NOXA A的表达，并描绘其与前列腺癌（PCa）recurrence.Experimental Design的关联：正常，前列腺上皮内瘤（PIN），前列腺癌敏感（HS）PCa，和前列腺癌难治性（HR）PCa组织被用来构建组织微阵列，包括共135例患者。两名观察员使用复合色标评估了NOXA和NOXA A免疫组织化学染色的强度。生成了180个递归分割和回归树（RPART）模型，以使用NOXA、CRYSTIA和临床参数预测HS癌症患者内的生化复发（BCR）。然后根据综合Brier评分（IBS）对模型进行排名。结果：NOXA表达的增加与PCa进展相关，在HR PCa中达到最高水平。在68%的HS癌症患者中观察到NOXA表达增加，并预测BCR（LR = 8.64; P = 0.003）。相比之下，HS癌症中的BCR-A表达最高，尽管70%的HS癌症患者表现出BCR-A表达增加，但单独的BCR-A不能预测BCR的发生。有趣的是，排名第一的RPART模型生成[IBS = 0.107; 95%置信区间（95%CI），0.065-0.128]包括手术切缘状态和NOXA和NOXA A表达，尽管前10个模型中获得的复发预后分类方案支持包含切缘状态、NOXA表达、和术前前列腺特异性抗原（PSA）（IBS = 0.114; 95%CI，0.069-0.142）。我们得出结论，NOXA和NOXA表达可能与PCa进展有关，并提出进一步验证生存树模型，包括手术切缘状态，NOXA表达，术前PSA预测BCR。
Purpose: To assess the expression of proapoptotic NOXA and PUMA in prostate tissues and delineate their association with prostate cancer (PCa) recurrence.Experimental Design: Normal, prostatic intraepithelial neoplasia (PIN), hormone-sensitive (HS) PCa, and hormone-refractory (HR) PCa tissues were used to build tissue microarrays encompassing a total of 135 patients. Two observers assessed the intensity of NOXA and PUMA immunohistochemical staining using a composite color scale. One hundred and eighty recursive partitioning and regression tree (RPART) models were generated to predict biochemical recurrence (BCR) within HS cancer patients using NOXA, PUMA, and clinical parameters. Models were then ranked according to the integrated Brier score (IBS).Results: Increasing NOXA expression was associated with PCa progression, reaching the highest levels in HR PCa. Increased NOXA expression was observed in 68% of HS cancer patients and was predictive of BCR (LR = 8.64; P = 0.003). In contrast, PUMA expression was highest in HS cancer, and although 70% of HS cancer patients exhibited increased PUMA expression, PUMA alone could not predict the onset of BCR. Interestingly, the top-ranking RPART model generated [IBS = 0.107; 95% confidence interval (95% CI), 0.065-0.128] included surgical margin status and NOXA and PUMA expression, although recurrent prognostic classification schemes obtained in the top 10 models favored a survival tree model containing margin status, NOXA expression, and preoperative prostate-specific antigen (PSA) (IBS = 0.114; 95% CI, 0.069-0.142).Conclusion: We conclude that NOXA and PUMA expression may be linked to PCa progression and propose further validation of a survival tree model including surgical margin status, NOXA expression, and preoperative PSA for predicting BCR.