Abstract：
BACKGROUND: Prostate cancer (PCa) remains one of the most complex tumors in men. The assessment of gene expression is expected to have a profound impact on cancer diagnosis, prognosis, and treatment decisions. The aim of this study was to determine the utility of the epithelial-mesenchymal transition (EMT) transcription factors Twist and Snai1 in the treatment of naïve prostate cancer.
RESULTS: We analyzed formalin-fixed paraffin-embedded (FFPE) prostate tissues from 108 PCa patients and 20 control biopsies using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and 2-ΔΔCt methods for Twist and Snail gene expression. The expression of Twist and Snai1 mRNA was significantly overexpressed in primary tissues of PCa patients compared with controls using ROC curve. Statistical analysis showed that the mRNAs of these two genes expression Snai1 and Twist were positively correlated with tumor development and prognostic parameters as Gleason score (p < 0.001; r = 0.707) and (p < 0.001; r = 0.627) respectively. The results of Kaplan-Meier analysis showed that mRNA expression of Snai1 and Twist genes expression were significant predictors of poor overall survival (OS) (Log rank p < 0.001) and progression-free survival (PFS) of patients (Log rank p < 0.001). Furthermore, our results showed that the expression of Snai1 and Twist genes expression in primary tissues of PCa patients could predict resistance to androgen deprivation therapy (p < 0.001) and resistance to the acidic drugs abiraterone or enzalutamide (p < 0.001). However, these two transcription factors failed to predict taxanes resistance at the time of diagnosis (p > 0.05).
CONCLUSIONS: These results suggest that Snai1 and Twist are overexpressed during the onset and progression of PCa malignancies and may be theranostic markers of resistance to ADT, abiraterone, or enzalutamide therapy.
RESULTS: We analyzed formalin-fixed paraffin-embedded (FFPE) prostate tissues from 108 PCa patients and 20 control biopsies using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and 2-ΔΔCt methods for Twist and Snail gene expression. The expression of Twist and Snai1 mRNA was significantly overexpressed in primary tissues of PCa patients compared with controls using ROC curve. Statistical analysis showed that the mRNAs of these two genes expression Snai1 and Twist were positively correlated with tumor development and prognostic parameters as Gleason score (p < 0.001; r = 0.707) and (p < 0.001; r = 0.627) respectively. The results of Kaplan-Meier analysis showed that mRNA expression of Snai1 and Twist genes expression were significant predictors of poor overall survival (OS) (Log rank p < 0.001) and progression-free survival (PFS) of patients (Log rank p < 0.001). Furthermore, our results showed that the expression of Snai1 and Twist genes expression in primary tissues of PCa patients could predict resistance to androgen deprivation therapy (p < 0.001) and resistance to the acidic drugs abiraterone or enzalutamide (p < 0.001). However, these two transcription factors failed to predict taxanes resistance at the time of diagnosis (p > 0.05).
CONCLUSIONS: These results suggest that Snai1 and Twist are overexpressed during the onset and progression of PCa malignancies and may be theranostic markers of resistance to ADT, abiraterone, or enzalutamide therapy.
摘要：
背景：前列腺癌（PCa）仍然是男性中最复杂的肿瘤之一。基因表达的评估有望对癌症诊断产生深远的影响，预后,和治疗决定。这项研究的目的是确定上皮-间质转化（EMT）转录因子Twist和Snai1在治疗初治前列腺癌中的应用。
结果：我们使用实时定量逆转录聚合酶链反应（RT-qPCR）和2-ΔΔCt方法分析了108例PCa患者的福尔马林固定石蜡包埋（FFPE）前列腺组织和20例对照活检组织的Twist和Snail基因表达。使用ROC曲线，与对照组相比，在PCa患者的原代组织中Twist和Snai1mRNA的表达明显过表达。统计分析表明，这两个基因表达Snai1和Twist的mRNA与肿瘤发展和预后参数呈正相关，分别为Gleason评分（p<0.001；r=0.707）和（p<0.001；r=0.627）。Kaplan-Meier分析结果表明，Snai1和Twist基因的mRNA表达是患者总体生存期（OS）（Logrankp<0.001）和无进展生存期（PFS）（Logrankp<0.001）的显着预测因子。此外，我们的结果表明，Snai1和Twist基因在PCa患者原代组织中的表达可以预测对雄激素剥夺治疗的抗性（p<0.001）和对酸性药物阿比特龙或恩扎鲁他胺的抗性（p<0.001）。然而,这两个转录因子在诊断时不能预测紫杉烷类的抗性(p>0.05)。
结论：这些结果表明，在PCa恶性肿瘤的发生和发展过程中，Snai1和Twist过度表达，可能是ADT耐药的诊断标志物，阿比特龙,或恩杂鲁胺治疗.
结果：我们使用实时定量逆转录聚合酶链反应（RT-qPCR）和2-ΔΔCt方法分析了108例PCa患者的福尔马林固定石蜡包埋（FFPE）前列腺组织和20例对照活检组织的Twist和Snail基因表达。使用ROC曲线，与对照组相比，在PCa患者的原代组织中Twist和Snai1mRNA的表达明显过表达。统计分析表明，这两个基因表达Snai1和Twist的mRNA与肿瘤发展和预后参数呈正相关，分别为Gleason评分（p<0.001；r=0.707）和（p<0.001；r=0.627）。Kaplan-Meier分析结果表明，Snai1和Twist基因的mRNA表达是患者总体生存期（OS）（Logrankp<0.001）和无进展生存期（PFS）（Logrankp<0.001）的显着预测因子。此外，我们的结果表明，Snai1和Twist基因在PCa患者原代组织中的表达可以预测对雄激素剥夺治疗的抗性（p<0.001）和对酸性药物阿比特龙或恩扎鲁他胺的抗性（p<0.001）。然而,这两个转录因子在诊断时不能预测紫杉烷类的抗性(p>0.05)。
结论：这些结果表明，在PCa恶性肿瘤的发生和发展过程中，Snai1和Twist过度表达，可能是ADT耐药的诊断标志物，阿比特龙,或恩杂鲁胺治疗.
