Clairefond Sylvie, Péant Benjamin, Ouellet Véronique, Barrès Véronique, Tian Zhe, Trudel Dominique, Karakiewicz Pierre I, Mes-Masson Anne-Marie, Saad Fred
Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM) et Institut du Cancer de Montréal (ICM), Montreal, QC H2X 0A9, Canada.
Département de Médecine, Faculté de Médecine, Université de Montréal, Montreal, QC H3T 1J4, Canada.
Cancers (Basel). 2020 Oct 29;12(11):3187. doi: 10.3390/cancers12113187.
Given that treatment decisions in prostate cancer (PC) are often based on risk, there remains a need to find clinically relevant prognostic biomarkers to stratify PC patients. We evaluated PUMA and NOXA expression in benign and tumor regions of the prostate using immunofluorescence techniques and determined their prognostic significance in PC.
PUMA and NOXA expression levels were quantified on six tissue microarrays (TMAs) generated from radical prostatectomy samples ( = 285). TMAs were constructed using two cores of benign tissue and two cores of tumor tissue from each patient. Association between biomarker expression and biochemical recurrence (BCR) at 3 years was established using log-rank (LR) and multivariate Cox regression analyses.
Kaplan-Meier analysis showed a significant association between BCR and extreme levels (low or high) of PUMA expression in benign epithelial cells (LR = 8.831, = 0.003). Further analysis revealed a significant association between high NOXA expression in benign epithelial cells and BCR (LR = 14.854, < 0.001). The combination of extreme PUMA and high NOXA expression identified patients with the highest risk of BCR (LR = 16.778, < 0.001) in Kaplan-Meier and in a multivariate Cox regression analyses (HR: 2.935 (1.645-5.236), < 0.001).
The combination of PUMA and NOXA protein expression in benign epithelial cells was predictive of recurrence following radical prostatectomy and was independent of PSA at diagnosis, Gleason score and pathologic stage.
鉴于前列腺癌（PC）的治疗决策通常基于风险，仍需要找到具有临床相关性的预后生物标志物来对PC患者进行分层。我们使用免疫荧光技术评估了前列腺良性和肿瘤区域中PUMA和NOXA的表达，并确定了它们在PC中的预后意义。
在由根治性前列腺切除术样本（n = 285）生成的六个组织微阵列（TMA）上对PUMA和NOXA的表达水平进行定量。每个患者的TMA使用两个良性组织芯和两个肿瘤组织芯构建。使用对数秩（LR）和多变量Cox回归分析确定生物标志物表达与3年时生化复发（BCR）之间的关联。
Kaplan-Meier分析显示，良性上皮细胞中PUMA表达的极端水平（低或高）与BCR之间存在显著关联（LR = 8.831，P = 0.003）。进一步分析显示，良性上皮细胞中高NOXA表达与BCR之间存在显著关联（LR = 14.854，P < 0.001）。在Kaplan-Meier分析和多变量Cox回归分析中（HR：2.935（1.645 - 5.236），P < 0.001），极端PUMA和高NOXA表达的组合识别出BCR风险最高的患者（LR = 16.778，P < 0.001）。
良性上皮细胞中PUMA和NOXA蛋白表达的组合可预测根治性前列腺切除术后的复发，且独立于诊断时的PSA、Gleason评分和病理分期。
