液体活检在前列腺癌进展监测中的研究进展

doi:10.3877/cma.j.issn.1674-3253.2025.05.003

前列腺癌是男性泌尿生殖系统最常见的恶性肿瘤之一，近年来总体生存期的延长预示着前列腺癌进入了慢性疾病管理阶段。在长期的治疗管理过程中，实时动态监测前列腺癌的进展，根据诊断及时调整治疗策略，对于患者总体生存期的进一步延长意义重大。液体活检作为一种非侵入性检测方法，通过采集患者的血液、脑脊液、唾液、胸水、腹水、尿液等液体，分析样本中的核酸、蛋白质等生物标志物，为临床决策提供信息。作为一种新兴的疾病诊断和监测工具，过去十年来，液体活检在肿瘤诊断、进展检测及预后评估领域充分展现了其微创性、可重复性、动态监测和操作简便的优势。本文就液体活检在前列腺癌进展监测中的最新研究进展进行论述。

关键词: 前列腺癌, 生物标志物, 液体活检, 去势抵抗, 进展监测

Prostate cancer is one of the most common malignant tumors in the male urogenital system, and the prolonged overall survival in recent years indicates that prostate cancer has entered the stage of chronic disease management. In the long-term treatment management process, real-time dynamic monitoring of prostate cancer progression and timely adjustment of treatment strategies based on diagnosis are of great significance for further prolonging the overall survival of patients. Liquid biopsy, as a non-invasive detection method, analyzes biomarkers such as nucleic acids and proteins in patients by collecting their blood, cerebrospinal fluid, saliva, pleural fluid, ascites, urine, and other fluids, providing information for clinical decision-making. As an emerging tool for disease diagnosis and monitoring, liquid biopsy has demonstrated its advantages in minimally invasive, reproducible, dynamic monitoring, and easy operation in the fields of tumor diagnosis, progression detection, and prognostic assessment over the past decade. This article discusses the latest research progress of liquid biopsy in monitoring the progression of prostate cancer.

Key words: Prostate cancer, Biomarker, Liquid biopsy, Castration resistance, Progress monitoring

表1 四项在前列腺癌进展监测中使用液体活检的临床研究

文献	研究指标	研究样本	研究类型	研究方法	结论
Chen等^[18]	血浆cfDNA	60份局限性PCa和175份mCRPC患者的血浆样本	屏障队列（基线和治疗过程中收集的样本）、VPC队列的mCRPC样本具有cfDNA测序谱，CPC（原发性）和WCDT（mCRPC）队列具有匹配组织的多组学测序数据	cfMeDIP-seq测序法，全基因组甲基化分析	建立了一个预测器可区分局限性PCa和mCRPC血浆样本
Annala等^[24]	血浆cfDNA	mCRPC患者的血浆样本	202例未经治疗的mCRPC患者被随机分为阿比特龙加泼尼松组（n=101），恩扎鲁胺组（n=101）	全外显子测序，Targeted 72-gene sequencing	验证了mCRPC对AR靶向治疗耐药的基因组驱动因素
Auvinen等^[39]	血浆外泌体	随机接受前列腺癌筛查男性的外周静脉血样本	男性被随机分为两组，一组为参加前列腺癌筛查的干预组，另一组为不予筛查的对照组。临床研究的主要结局是随访10年和15年的前列腺癌死亡率	基于随机分配的研究人群，筛查的效果量化为干预组与对照组之间的风险差异	目前尚无主要结局数据
Stuopelyte等^[45]	尿液miRNA	237例PCa患者的标本（组织和/或尿液）、23例前列腺增生（BPH）患者和62例无症状对照男性的尿液标本	组织样本分为两组，PCa（n=56）以及非前列腺癌组织（n=16）；尿液样本被分为四组，PCa1（n=143），PCa2（n=72），BPH（n=23），ASC（n=62），PCa1队列平均随访时间为2.7年，收集了91.6%（143例中131例）病例的随访数据。PCa2组平均随访时间较短（1.0年），72例患者中有18例缺少随访数据	RT-qPCR数据预处理、分析验证、归一化和统计分析	定量检测尿miR-148a和miR-375可作为一种无创、灵敏、特异检测前列腺癌的工具

表1 四项在前列腺癌进展监测中使用液体活检的临床研究

文献	研究指标	研究样本	研究类型	研究方法	结论
Chen等^[18]	血浆cfDNA	60份局限性PCa和175份mCRPC患者的血浆样本	屏障队列（基线和治疗过程中收集的样本）、VPC队列的mCRPC样本具有cfDNA测序谱，CPC（原发性）和WCDT（mCRPC）队列具有匹配组织的多组学测序数据	cfMeDIP-seq测序法，全基因组甲基化分析	建立了一个预测器可区分局限性PCa和mCRPC血浆样本
Annala等^[24]	血浆cfDNA	mCRPC患者的血浆样本	202例未经治疗的mCRPC患者被随机分为阿比特龙加泼尼松组（n=101），恩扎鲁胺组（n=101）	全外显子测序，Targeted 72-gene sequencing	验证了mCRPC对AR靶向治疗耐药的基因组驱动因素
Auvinen等^[39]	血浆外泌体	随机接受前列腺癌筛查男性的外周静脉血样本	男性被随机分为两组，一组为参加前列腺癌筛查的干预组，另一组为不予筛查的对照组。临床研究的主要结局是随访10年和15年的前列腺癌死亡率	基于随机分配的研究人群，筛查的效果量化为干预组与对照组之间的风险差异	目前尚无主要结局数据
Stuopelyte等^[45]	尿液miRNA	237例PCa患者的标本（组织和/或尿液）、23例前列腺增生（BPH）患者和62例无症状对照男性的尿液标本	组织样本分为两组，PCa（n=56）以及非前列腺癌组织（n=16）；尿液样本被分为四组，PCa1（n=143），PCa2（n=72），BPH（n=23），ASC（n=62），PCa1队列平均随访时间为2.7年，收集了91.6%（143例中131例）病例的随访数据。PCa2组平均随访时间较短（1.0年），72例患者中有18例缺少随访数据	RT-qPCR数据预处理、分析验证、归一化和统计分析	定量检测尿miR-148a和miR-375可作为一种无创、灵敏、特异检测前列腺癌的工具

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Research progress of liquid biopsy in monitoring the progression of prostate cancer

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Research progress of liquid biopsy in monitoring the progression of prostate cancer