Authors
Kevin J Liu, William Y Shi, Monica C Nesselbush, Nick A Phillips, Kathleen E Mach, Bogdan Luca, Ravi K Bajpai, Isabel Jabara, Jordan C Cheng, Takeshi Sugio, Navika Shukla, Emily C Shen, Ivy Lee Koh, Douglas J Wu, Chih-Long Liu, Diego Almanza, Soyeong Jun, Feng Tian, Emily G Hamilton, Christian R Hoerner, Rui Wang, Mohammad S Esfahani, Angela Hui, Vinh La, Grace Holton, Gabriela Rodriguez, Timothy J Lee, Xi Ling, Nikitha Kalahasti, Spoorthi Vallamkonda, Patrick Mullane, Simon B Chen, Eugene Shkolyar, Kris Prado, Ali Raza Khaki, Emily Chan, Mark K Buyyounouski, Alice C Fan, Eila C Skinner, Ash A Alizadeh, Joseph C Liao, Maximilian Diehn
Published in
Nature medicine. Oct 02, 2026. Epub Oct 02, 2026.
Abstract
Urine biomarkers promise to improve noninvasive detection and molecular characterization of genitourinary malignancies. Here we describe urine random priming and affinity capture of cell-free RNA (cfRNA) fragments for enrichment analysis by sequencing (uRARE-seq), a liquid biopsy method for urine cfRNA profiling, and apply it to 683 urine samples from patients with cancer and controls. Urine cfRNA contained transcripts from genitourinary tissues and, in patients with prostate, kidney or bladder cancer, tumor-derived transcripts. uRARE-seq demonstrated 95% sensitivity at 90% specificity for detecting localized bladder cancer. The method outperformed urine tumor DNA analysis and was unaffected by the presence of field-effect mutations. Urine cfRNA analysis also sensitively detected minimal residual disease and distinguished complete molecular responses after surgery from those after intravesical Bacillus Calmette-Guérin (BCG). Pretreatment urine from complete responders to BCG was enriched for T cell and other immune signatures, suggesting a preexisting antitumor immune response, whereas nonresponders showed higher expression of proliferation-related genes. In pretreatment urine from 114 patients, this biological difference enabled development of a biomarker predicting likelihood of response to BCG versus chemotherapy (area under the curve 0.93) that was strongly associated with risk of recurrence. Urine cfRNA analysis is therefore a promising biomarker approach for bladder cancer and potentially other urologic malignancies, although prospective studies are needed to assess its clinical utility.
PMID:
42827132
Bibliographic data and abstract were imported from PubMed on 03 Oct 2026.
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