美国斯坦福大学Maximilian Diehn小组开发出场效应提示膀胱癌的尿液活检。2026年1月27日出版的《细胞》杂志发表了这项成果。

课题组表明，尿中体细胞突变的患病率随着年龄的增长而增加。该课题组研究人员介绍了一种改进的utDNA最小残留病（MRD）方法，通过去除场效应突变来增加特异性。将这种场效应信息MRD方法应用于261例接受手术和辅助卡介苗治疗的NMIBC患者样本，该课题组研究人员确定了三种分子反应类别，包括手术反应者、卡介苗反应者和无反应者。对两种治疗反应的分子预测因子不同，卡介苗中存在预先存在的免疫激活和较高的突变负担，而手术应答者则没有。这些发现强调了场效应液体活检方法在指导个性化治疗和发现多模式治疗中单个成分的生物标志物方面的潜力。

据了解，只有一些非侵袭性膀胱癌（NMIBC）患者受益于膀胱内卡介苗（BCG），预测性生物标志物仍然缺乏。虽然尿肿瘤DNA （utDNA）分析很有希望，但肿瘤邻近正常尿路上皮的突变，即场效应，限制了特异性。

附：英文原文

Title: Field-effect-informed urine liquid biopsy for bladder cancer

Author: William Y. Shi, Kevin J. Liu, Mohammad S. Esfahani, Kathleen E. Mach, Nick A. Phillips, Diego Almanza, Ravi K. Bajpai, Joseph G. Schroers-Martin, Ludimila Trabanino, Timothy J. Lee, Vinh La, Gabriela Rodriguez, Grace Holton, Simon B. Chen, Patrick Mullane, Douglas J. Wu, Monica C. Nesselbush, Takeshi Sugio, Jordan C. Cheng, Isabel Jabara, Emily G. Hamilton, Stefan K. Alig, Chih-Long Liu, Dylan J. Peterson, Kris Prado, Eugene Shkolyar, Alan Thong, Jay B. Shah, Harcharan Gill, Christian A. Kunder, Emily Chan, Ali Raza Khaki, Eila C. Skinner, Ash A. Alizadeh, Joseph C. Liao, Maximilian Diehn

Issue&Volume: 2026-01-27

Abstract: Only some non-muscle-invasive bladder cancer (NMIBC) patients benefit from intravesical Bacillus Calmette-Guérin (BCG), and predictive biomarkers remain lacking. While urine tumor DNA (utDNA) analysis is promising, mutations in tumor-adjacent normal urothelium, namely the field effect, limit specificity. Here, we show that the prevalence of somatic mutations in the urine increases with age. We introduce an improved utDNA minimal residual disease (MRD) approach that increases specificity by removing field-effect mutations. Applying this field-effect-informed MRD approach to 261 samples from NMIBC patients undergoing surgery and adjuvant BCG, we identify three molecular response classes, including surgical responders, BCG responders, and non-responders. Molecular predictors of response to the two treatments differ, with pre-existing immune activation and higher mutation burden enriched in BCG but not surgery responders. These findings highlight the potential of field-effect-informed liquid biopsy methods for guiding personalized therapy and uncovering biomarkers for individual components of multimodal treatments.

DOI: 10.1016/j.cell.2025.12.054

Source: https://www.cell.com/cell/abstract/S0092-8674(25)01503-X