Cell-Free DNA in Urine: A New Biomarker for UTUC Detection

Urine cfDNA is a promising biomarker for upper tract urothelial carcinoma (UTUC), showing a strong correlation with tissue DNA.

Cell-free DNA (cfDNA) is one of the important biomarkers of liquid biopsy for many malignant cancers like urothelial bladder cancer.

However, the use of cfDNA in upper tract urothelial carcinoma (UTUC) and voided urine cfDNA for tumor detection is unexplored. Dr. Alexander Zhu discussed the role of voided urine cell-free DNA as a biomarker for upper tract urothelial carcinoma (UTUC) in the 2024 Society of Urologic Oncology (SUO) annual meeting held in Dallas, between December 3 and December 6, 2024 ().

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‘Did you know
Upper tract urothelial carcinoma (UTUC) is a rare malignant tumor. #UTUC #cancer #urothelialcancer #medindia ’

cfDNA Biomarkers for UTUC

The study aimed to assess the reliability of urine or plasma cfDNA as a biomarker for UTUC using low-pass whole genome sequencing (LP-WGS). Four patients participated in the study with known or suspected UTUC undergoing nephroureterectomy. Peripheral blood and voided urine samples were collected from all the patients before surgery. cfDNA was isolated from urine and plasma samples using standard protocols.

cfDNA was isolated from urine and plasma using standard protocols. Genomic DNA was extracted from radical nephroureterectomy specimens and established as tissue DNA. Next-generation sequencing using LP-WGS was performed on all samples (urine, plasma, tissue) to a minimum depth of 0.1x. Sequenced reads were matched against the human reference genome (hg19).

With the help of a bioinformatic tool, copy number alterations (CNAs) were identified. Copy number alterations are genomic regions of the samples deviated from the identified reference genome.

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Urine vs. Plasma cfDNA in UTUC Detection

CNAs of urine and plasma were matched with tissue samples and the differences in CNAs at the chromosomal and sub-chromosomal levels were identified among all three sample types.

Four patients underwent radical nephroureterectomy with preoperative voided urine cfDNA, preoperative plasma cfDNA, and tumor tissue DNA available for analysis. The pathology results were pT1N0 (n=2) and pT2Nx (n=2). At the chromosomal level, CNAs in urine cfDNA closely mirrored that of a tissue.

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The correlation coefficients for chromosomal abnormalities between urine vs. tissue ranged from 0.873 to 0.997. However, this correlation was not observed in Plasma cfDNA and tissue samples.

Dr. Alex Zhu concluded their poster by noting several key findings that cfDNA for UTUC, CNAs of urine cfDNA closely mirrored those of tissue samples. However, the same relationship was not observed between plasma cfDNA and tissue samples. These findings serve as proof of concept that UTUC can be detected in urine supernatant using LP-WGS.

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The data suggest that urine cfDNA has the potential to serve as an accurate biomarker for UTUC, offering a less invasive yet equally informative approach to UTUC diagnosis and surveillance.

Reference:

Toward urinary cell-free DNA-based treatment of urothelial carcinoma: a narrative review - (https://pmc.ncbi.nlm.nih.gov/articles/PMC8100839/)

Source-Medindia