Chen Gang, Jia Guojin, Chao Fan, Xie Feng, Zhang Yue, Hou Chuansheng, Huang Yong, Tang Haoran, Yu Jianjun, Zhang Jihong, Jia Shidong, Xu Guoxiong
Department of Urology, Jinshan Hospital, Fudan University, Shanghai, China.
Huidu Shanghai Medical Sciences Ltd, Shanghai, China.
Front Oncol. 2022 Mar 23;12:759791. doi: 10.3389/fonc.2022.759791. eCollection 2022.
Prostate cancer (PCa) is one of the most common malignant tumors, accounting for 20% of total tumors ranked first in males. PCa is usually asymptomatic at the early stage and the specificity of the current biomarkers for the detection of PCa is low. The present study evaluates circulating tumor DNA (ctDNA) in blood or urine, which can be used as biomarkers of PCa and the combination of these markers may increase the sensitivity and specificity of the detection of PCa.
Tissue, blood, and urine samples were collected from patients with PCa. All prostate tissue specimens underwent pathological examination. A hybrid-capture-based next-generation sequencing assay was used for plasma and urinary ctDNA profiling. Sequencing data were analyzed by an in-house pipeline for mutation calling. Mutational profiles of PCa and BPH were compared in both plasma and urine samples. Associations of detected mutations and clinical characteristics were statistically analyzed.
A significant association of mutation allele frequencies (MAFs) in the blood samples with patients with metastatic PCa rather than patients with primary PCa, and MAFs are changed after treatment in patients with PCa. Further, the number of mutations in urine is not associated with clinical characteristics of PCa patients, but the frequencies of mutation alleles in the urine are associated with patient age. Comparison of cfDNA aberration profiles between urine and blood reveals more alterations in urine than in blood, including , , , , and mutations.
This work provides the potential clinical application of urine, in addition to blood, as a powerful and convenient non-invasive approach in personalized medicine for patients with PCa.
前列腺癌（PCa）是最常见的恶性肿瘤之一，占男性肿瘤总数的20%，位居首位。PCa早期通常无症状，目前用于检测PCa的生物标志物特异性较低。本研究评估血液或尿液中的循环肿瘤DNA（ctDNA），其可作为PCa的生物标志物，这些标志物的组合可能会提高PCa检测的敏感性和特异性。
收集PCa患者的组织、血液和尿液样本。所有前列腺组织标本均进行病理检查。采用基于杂交捕获的下一代测序分析方法对血浆和尿液中的ctDNA进行分析。测序数据通过内部流程进行突变检测分析。比较血浆和尿液样本中PCa和良性前列腺增生（BPH）的突变谱。对检测到的突变与临床特征的相关性进行统计学分析。
血液样本中的突变等位基因频率（MAFs）与转移性PCa患者而非原发性PCa患者显著相关，且PCa患者治疗后MAFs发生变化。此外，尿液中的突变数量与PCa患者的临床特征无关，但尿液中突变等位基因的频率与患者年龄相关。尿液和血液中游离DNA（cfDNA）畸变谱的比较显示，尿液中的改变比血液中更多，包括 、 、 、 和 突变。
这项工作为尿液除血液之外作为PCa患者个性化医疗中一种强大且便捷的非侵入性方法提供了潜在的临床应用。
