Genomic mutation profiling using liquid biopsy in Korean patients with prostate cancer: Circulating tumor DNA mutation predicts the development of castration resistance

• Published in: Investigative and clinical urology Vol. 62; no. 2; pp. 224 - 232
• Main Authors: Yu, Jiwoong, Cho, Eunhae, Choi, Joongwon, Lim, Joung Eun, Lee, Junnam, Kang, Minyong, Sung, Hyun Hwan, Jeong, Byong Chang, Seo, Seong Il, Jeon, Seong Soo, Lee, Hyun Moo, Jeon, Hwang Gyun
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Urological Association 01.03.2021; Korean Urological Association; 대한비뇨의학회
• Subjects: Aged; biomarkers; castration-resistant; circulating tumor dna; Circulating Tumor DNA - genetics; Genome; Humans; Liquid Biopsy; Male; Mutation; Original; Prognosis; prostatic neoplasms; Prostatic Neoplasms, Castration-Resistant - genetics; Prostatic Neoplasms, Castration-Resistant - pathology; Republic of Korea; Retrospective Studies; 비뇨기과학; Republic of Korea; Biomarkers; Prostatic neoplasms; Circulating tumor DNA; Prostatic neoplasms, castration-resistant
• ISSN: 2466-0493; 2466-054X
• DOI: 10.4111/ICU.20200406

To investigate germline and somatic mutation profiles in Korean patients with prostate cancer using liquid biopsy and solid tissue testing and to evaluate the prognostic value of circulating tumor DNA (ctDNA) in predicting castration resistance in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Plasma samples from 56 prostate cancer patients were subjected to next-generation sequencing (NGS) to identify germline mutations and ctDNA analysis using liquid biopsy to detect somatic mutations. Additionally, paired solid cancer tissues from 18 patients were subject to NGS to detect somatic mutations. The clinical parameters and ctDNA profiles of patients with mHSPC were analyzed to evaluate the prognostic value of ctDNA mutations with respect to predicting castration resistance using Cox proportional hazards regression analysis. Germline mutations occurred in 3.6% of the patients in this cohort, with mutations identified in (1.8%) and (1.8%). Somatic mutations detected by liquid biopsy and solid tissue testing were common in (12.5%), (3.6%), and (3.6%). Of the 18 patients with paired tissue testing, two patients had at least one identical somatic mutation in both the liquid biopsy and solid tissue testing. In patients with mHSPC, the presence of ctDNA mutations could independently predict the castration resistance development (hazard ratio, 13.048; 95% confidential interval, 1.109-153.505; p=0.041). Korean patients with prostate cancer showed a relatively low germline mutation rate compared to other ethnicities. The ctDNA mutations detected by liquid biopsy can predict the development of castration resistance in patients with mHSPC.