PUMA and NOXA Expression in Tumor-Associated Benign Prostatic Epithelial Cells Are Predictive of Prostate Cancer Biochemical Recurrence.
PUMA and NOXA Expression in Tumor-Associated Benign Prostatic Epithelial Cells Are Predictive of Prostate Cancer Biochemical Recurrence.
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DOI：
10.3390/cancers12113187
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发表时间：
2020-10-29
期刊：
影响因子：
5.2
通讯作者：
Saad F
中科院分区：
文献类型：
--
作者：
Clairefond S;Péant B;Ouellet V;Barrès V;Tian Z;Trudel D;Karakiewicz PI;Mes-Masson AM;Saad F
在接受前列腺癌诊断后，患者根据肿瘤分级、分期和前列腺特异性抗原(PSA)水平遵循常规治疗计划。然而，对其他癌症的研究表明，使用生物标记物进行个性化治疗的重要性。由于目前还没有批准的生物标记物用于前列腺癌，临床上有必要开发这样的分层工具。在这里，我们的研究表明，PUMA和NOXA是具有很高预后价值的标志物，当观察它们在前列腺内的良性腺体和肿瘤腺体中的存在时。因此，这些标记物的存在可能有助于更好地预测诊断结果。将这些标记物纳入临床实践可能最终导致新诊断患者的选择性治疗选择。这反过来应导致更好的癌症控制，潜在地降低前列腺癌的发病率和死亡率。背景：鉴于前列腺癌(PC)的治疗决策通常基于风险，仍有必要找到临床上相关的预后生物标记物来对PC患者进行分层。我们用免疫荧光技术检测PUMA和NOXA在前列腺癌中的表达，并确定它们在前列腺癌中的预后意义。方法：对285例前列腺癌根治术标本制作的6个组织芯片(TMA)上的PUMA和NOXA的表达水平进行定量研究。TMA是用来自每个患者的两个良性组织核心和两个肿瘤组织核心构建的。生物标记物的表达与3年生化复发(BCR)之间的关系采用对数秩次(LR)和多因素COX回归分析。结果：Kaplan-Meier分析显示良性上皮细胞中bcr与PUMA表达的极端水平(低或高)显著相关(LR=8.831，p=0.003)。进一步分析发现良性上皮细胞中NOXA的高表达与bcr显著相关(LR=14.854，p<；0.001)。在Kaplan-Meier和多变量COX回归分析中，极端PUMA和高NOXA表达相结合，确定了bcr风险最高的患者(LR=16.778，p<；0.001)(HR：2.935(1.645-5.236)，p<；0.001)。结论：PUMA和NOXA蛋白在良性上皮细胞中的联合表达可预测前列腺癌根治术后复发，且与PSA的诊断、Gleason评分和病理分期无关。
After receiving a diagnosis of prostate cancer, patients follow a routine treatment plan based on tumor grade, stage and prostate-specific antigen (PSA) level. However, studies in other cancers have shown the importance of using biomarkers to personalize treatments. With no approved biomarkers presently in use in prostate cancer, there is a clinical need to develop such stratification tools. Here our study shows that PUMA and NOXA are markers that have a high prognostic value when looking at their presence in both benign and tumor glands within the prostate. Hence, the presence of these markers may help to better predict outcomes at diagnosis. Incorporating these markers into clinical practice may eventually lead to selective treatment options in newly diagnosed patients. This in turn should lead to better cancer control, potentially lowering the morbidity and mortality due to prostate cancer. Background: 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. Methods: PUMA and NOXA expression levels were quantified on six tissue microarrays (TMAs) generated from radical prostatectomy samples (n = 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. Results: 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, p = 0.003). Further analysis revealed a significant association between high NOXA expression in benign epithelial cells and BCR (LR = 14.854, p < 0.001). The combination of extreme PUMA and high NOXA expression identified patients with the highest risk of BCR (LR = 16.778, p < 0.001) in Kaplan–Meier and in a multivariate Cox regression analyses (HR: 2.935 (1.645–5.236), p < 0.001). Conclusions: 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.
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影响因子：
3.7
作者：
Labouba I;Le Page C;Communal L;Kristessen T;You X;Péant B;Barrès V;Gannon PO;Mes-Masson AM;Saad F
通讯作者：
Saad F
影响因子：
11.5
作者：
Diallo, Jean-Simon;Aldejmah, Abdulhadi;Saad, Fred
通讯作者：
Saad, Fred
影响因子：
2.1
作者：
QUINLAN, DM;PARTIN, AW;WALSH, PC
通讯作者：
WALSH, PC
影响因子：
56.9
作者：
Villunger, A;Michalak, EM;Strasser, A
通讯作者：
Strasser, A
影响因子：
8.3
作者：
Hikisz P;Kiliańska ZM
通讯作者：
Kiliańska ZM