Abstract

Although prostate cancer (PCa) is one of the most common tumors in European males, the only minimally invasive diagnostic tool in PCa setup is the determination of PSA in serum. Cell-free DNA (cfDNA) has been demonstrated to be helpful for PCa diagnosis but has not yet been integrated into the clinical setting. This review aims to provide a systematic update of cfDNA and its fragmentation patterns in PCa reported in literature published over the last twenty years. Due to the high variability of the scientific methods adopted and a lack of standardized median cfDNA levels, results fluctuate across different studies. These differences may be due to the cfDNA source, the quantification method, or the fragmentation pattern. Blood plasma is the most frequently analyzed biological fluid, but seminal plasma has been reported to contain higher cfDNA concentration due to its vicinity to the tumor origin. CfDNA has been shown to be composed of single-stranded (ssDNA) and double-stranded DNA (dsDNA), so the total cfDNA concentration should be preferred as it corresponds best to the tumor mass. Fluorometry and capillary electrophoresis (CE) may be quick and cost-effective tools for cfDNA assessment in a clinical setting. The greatest future challenge is the elaboration of common guidelines and standardized procedures for diagnostic laboratories performing cfDNA analysis. A multiparametric approach combining the analysis of total cfDNA (both ssDNA and dsDNA), cfDNA fragment length, and specific genetic mutations (ctDNA assessment) is required for optimal future applications of liquid biopsy.

摘要

尽管前列腺癌 (PCa) 是欧洲男性中最常见的肿瘤之一，但 PCa 设置中唯一的微创诊断工具是测定血清中的 PSA。无细胞 DNA (cfDNA) 已被证明有助于 PCa 诊断，但尚未整合到临床环境中。本综述旨在对过去 20 年发表的文献中报道的 PCa 中 cfDNA 及其片段化模式进行系统更新。由于所采用的科学方法的高度可变性以及缺乏标准化的 cfDNA 中值水平，不同研究的结果会有所波动。这些差异可能是由于 cfDNA 来源、定量方法或碎片模式造成的。血浆是最常被分析的生物体液，但据报道，由于靠近肿瘤起源，精浆含有更高的 cfDNA 浓度。CfDNA 已被证明由单链 (ssDNA) 和双链 DNA (dsDNA) 组成，因此应首选总 cfDNA 浓度，因为它最适合肿瘤块。荧光测定法和毛细管电泳 (CE) 可能是临床环境中 cfDNA 评估的快速且经济高效的工具。未来最大的挑战是为执行 cfDNA 分析的诊断实验室制定通用指南和标准化程序。液体活检的最佳未来应用需要结合总 cfDNA（ssDNA 和 dsDNA）、cfDNA 片段长度和特定基因突变（ctDNA 评估）分析的多参数方法。