Ishibashi Yusuke, Tobisawa Yuki, Hatakeyama Shingo, Ohashi Tetsu, Tanaka Masakazu, Narita Shintaro, Koie Takuya, Habuchi Tomonori, Nishimura Shin-Ichiro, Ohyama Chikara, Yoneyama Tohru
Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Prostate. 2014 Nov;74(15):1521-9. doi: 10.1002/pros.22869. Epub 2014 Aug 23.
The U.S. FDA has approved several novel systemic agents including abiraterone acetate and taxoid cabazitaxel for metastatic castration-resistant prostate cancer (CRPC) result in a complicated decision-making while selecting an appropriate treatment. Therefore, a predictive biomarker for CRPC would provide useful information to physicians. The aim of this study is to evaluate the diagnostic potential of serum N-glycan profiling in CRPC.
Serum N-glycomics was performed in 80 healthy volunteers and 286 benign prostatic hyperplasia, 258 early-stage PC, 46 PC with androgen deprivation therapy (ADT), and 68 CRPC patients using the glycoblotting method. A total of 36 types of N-glycan levels in each patient were analyzed using logistic regression analysis and receiver operating characteristic curves. We also examined the expression of N-glycan branching enzyme genes in PC cell lines using quantitative RT-PCR.
We observed that tri- and tetra-antennary N-glycans were significantly higher in CRPC patients than in any other groups. The longitudinal follow-up of tri- and tetra- antennary N-glycan levels revealed that one PC with ADT patient showed an increase that was more than the cut-off level and two consecutive increases in tri- and tetra-antennary N-glycan levels 3 months apart; resulted in biochemical recurrence despite the castrate level of testosterone, and the patient was defined as CRPC. Expression of N-glycan branching enzyme genes were significantly upregulated in CRPC cell lines.
These results suggest that the overexpression of tri- and tetra-antennary N-glycan may be associated with the castration-resistant status in PC and may be a potential predictive biomarker for CRPC.
美国食品药品监督管理局(FDA)已批准了几种新型全身用药,包括醋酸阿比特龙和紫杉烷类卡巴他赛,用于治疗转移性去势抵抗性前列腺癌(CRPC),这使得在选择合适的治疗方法时决策变得复杂。因此,CRPC的预测生物标志物可为医生提供有用信息。本研究旨在评估血清N-聚糖谱在CRPC中的诊断潜力。
采用糖印迹法对80名健康志愿者、286例良性前列腺增生患者、258例早期前列腺癌患者、46例接受雄激素剥夺治疗(ADT)的前列腺癌患者以及68例CRPC患者进行血清N-糖组学分析。使用逻辑回归分析和受试者工作特征曲线分析每位患者共36种N-聚糖水平。我们还使用定量逆转录聚合酶链反应(RT-PCR)检测前列腺癌细胞系中N-聚糖分支酶基因的表达。
我们观察到,CRPC患者的三触角和四触角N-聚糖明显高于其他任何组。对三触角和四触角N-聚糖水平的纵向随访显示,1例接受ADT的前列腺癌患者的N-聚糖水平升高超过临界值,且三触角和四触角N-聚糖水平在3个月内连续两次升高;尽管睾酮水平处于去势状态,但仍发生了生化复发,该患者被定义为CRPC。CRPC细胞系中N-聚糖分支酶基因的表达明显上调。
这些结果表明,三触角和四触角N-聚糖的过表达可能与前列腺癌的去势抵抗状态有关,可能是CRPC的潜在预测生物标志物。