Januskevicius Tomas, Sabaliauskaite Rasa, Dabkeviciene Daiva, Vaicekauskaite Ieva, Kulikiene Ilona, Sestokaite Agne, Vidrinskaite Asta, Bakavicius Arnas, Jankevicius Feliksas, Ulys Albertas, Jarmalaite Sonata
Clinic of Gastroenterology, Nephro-Urology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, M. K. Ciurlionio st. 21/27, LT-03101 Vilnius, Lithuania.
Laboratory of Genetic Diagnostic, National Cancer Institute, Santariskiu st. 1, LT-08406 Vilnius, Lithuania.
Biomedicines. 2023 Mar 2;11(3):761. doi: 10.3390/biomedicines11030761.
(1) Background: DNA damage response (DDR) pathway gene mutations are detectable in a significant number of patients with metastatic castration-resistant prostate cancer (mCRPC). The study aimed at identification of germline and/or somatic DDR mutations in blood and urine samples from patients with mCRPC for correlation with responses to entire sequence of systemic treatment and survival outcomes. (2) Methods: DDR gene mutations were assessed prospectively in DNA samples from leukocytes and urine sediments from 149 mCRPC patients using five-gene panel targeted sequencing. The impact of DDR status on progression-free survival, as well as treatment-specific and overall survival, was evaluated using Kaplan-Meier curves and Cox regression. (3) Results: DDR mutations were detected in 16.6% of urine and 15.4% of blood samples. , , and mutations were associated with significantly shorter PFS in response to conventional androgen deprivation therapy and first-line mCRPC therapy with abiraterone acetate. Additionally, and mutation-bearing patients had a significantly worse response to radium-223. However, DDR mutation status was predictive for the favourable effect of second-line abiraterone acetate after previous taxane-based chemotherapy. (4) Conclusions: Our data confirm the benefit of non-invasive urine-based genetic testing for timely identification of high-risk prostate cancer cases for treatment personalization.
(1) 背景：在大量转移性去势抵抗性前列腺癌（mCRPC）患者中可检测到DNA损伤反应（DDR）通路基因突变。本研究旨在鉴定mCRPC患者血液和尿液样本中的种系和/或体细胞DDR突变，以与全身治疗的整个序列反应和生存结果相关联。(2) 方法：使用五基因panel靶向测序对149例mCRPC患者白细胞和尿沉渣的DNA样本中的DDR基因突变进行前瞻性评估。使用Kaplan-Meier曲线和Cox回归评估DDR状态对无进展生存期以及特定治疗和总生存期的影响。(3) 结果：在16.6%的尿液样本和15.4%的血液样本中检测到DDR突变。 、 、 和 突变与接受传统雄激素剥夺治疗和一线醋酸阿比特龙治疗的mCRPC患者的无进展生存期显著缩短相关。此外，携带 和 突变的患者对镭-223的反应明显更差。然而，DDR突变状态可预测先前基于紫杉烷化疗后二线醋酸阿比特龙的有利效果。(4) 结论：我们的数据证实了基于尿液的非侵入性基因检测对于及时识别高危前列腺癌病例以实现治疗个性化的益处。
