Tjon-Kon-Fat Lee-Ann, Lundholm Marie, Schröder Mona, Wurdinger Thomas, Thellenberg-Karlsson Camilla, Widmark Anders, Wikström Pernilla, Nilsson Rolf Jonas Andreas
Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden.
Department of Medical Biosciences, Pathology, Umea University, Umea, Sweden.
Prostate. 2018 Jan;78(1):48-53. doi: 10.1002/pros.23443. Epub 2017 Nov 2.
Novel therapies for castration resistant prostate cancer (CRPC) have been introduced in the clinic with possibilities for individualized treatment plans. Best practice of those expensive drugs requires predictive biomarker monitoring. This study used circulating biomarker analysis to follow cancer-derived transcripts implicated in therapy resistance.
The isolated platelet population of blood samples and digital-PCR were used to identify selected biomarker transcripts in patients with CRPC prior chemo- or androgen synthesis inhibiting therapy.
Fifty patients received either docetaxel (n = 24) or abiraterone (n = 26) therapy, with therapy response rates of 54% and 48%, respectively. Transcripts for the PC-associated biomarkers kallikrein-related peptidase-2 and -3 (KLK2, KLK3), folate hydrolase 1 (FOLH1), and neuropeptide-Y (NPY) were uniquely present within the platelet fraction of cancer patients and not detected in healthy controls (n = 15). In the abiraterone treated cohort, the biomarkers provided information on therapy outcome, demonstrating an association between detectable biomarkers and short progression free survival (PFS) (FOLH1, P < 0.01; KLK3, P < 0.05; and NPY, P < 0.05). Patients with biomarker-negative platelets had the best outcome, while FOLH1 (P < 0.05) and NPY (P = 0.05) biomarkers provided independent predictive information in a multivariate analysis regarding PFS. KLK2 (P < 0.01), KLK3 (P < 0.001), and FOLH1 (P < 0.05) biomarkers were associated with short overall survival (OS). Combining three biomarkers in a panel (KLK3, FOLH1, and NPY) made it possible to separate long-term responders from short-term responders with 87% sensitivity and 82% specificity.
Analyzing tumor-derived biomarkers in platelets of CRPC patients enabled prediction of the outcome after abiraterone therapy with higher accuracy than baseline serum PSA or PSA response.
去势抵抗性前列腺癌（CRPC）的新型疗法已应用于临床，为个性化治疗方案提供了可能。对于这些昂贵药物的最佳应用需要进行预测性生物标志物监测。本研究采用循环生物标志物分析来追踪与治疗抵抗相关的肿瘤来源转录本。
利用血液样本中分离出的血小板群体和数字PCR技术，在接受化疗或雄激素合成抑制治疗前的CRPC患者中鉴定特定的生物标志物转录本。
50例患者分别接受多西他赛（n = 24）或阿比特龙（n = 26）治疗，治疗有效率分别为54%和48%。前列腺癌相关生物标志物激肽释放酶相关肽酶-2和-3（KLK2、KLK3）、叶酸水解酶1（FOLH1）和神经肽Y（NPY）的转录本仅在癌症患者的血小板部分中存在，在健康对照者（n = 15）中未检测到。在阿比特龙治疗组中，这些生物标志物提供了有关治疗结果的信息，显示可检测的生物标志物与较短的无进展生存期（PFS）之间存在关联（FOLH1，P < 0.01；KLK3，P < 0.05；NPY，P < 0.05）。血小板生物标志物阴性的患者预后最佳，而在关于PFS的多变量分析中，FOLH1（P < 0.05）和NPY（P = 0.05）生物标志物提供了独立的预测信息。KLK2（P < 0.01）、KLK3（P < 0.001）和FOLH1（P < 0.05）生物标志物与较短的总生存期（OS）相关。将三种生物标志物组合成一个面板（KLK3、FOLH1和NPY）能够以87%的敏感性和82%的特异性区分长期应答者和短期应答者。
分析CRPC患者血小板中的肿瘤来源生物标志物能够比基线血清PSA或PSA应答更准确地预测阿比特龙治疗后的结果。
