Urine-Based Liquid Biopsy for Nonurological Cancers

Abstract

Aims: The use of circulating cell-free DNA for detection of cancer genetics has been studied extensively. Liquid biopsy often refers to the use of blood as a minimally invasive source of body fluid for detecting circulating tumor DNA (ctDNA). However, urine collection, which is completely noninvasive, has been shown to also have great promise to serve as an alternate body fluid source for ctDNA. In this review article, we focus on the clinical utility of urine for genetic liquid biopsy of nonurological cancers.

Conclusion: Although still in early stages as compared with blood-based liquid biopsy, recent studies have demonstrated the value of urine-based liquid biopsies for: nonurological cancer screening; early detection; monitoring for recurrence and metastasis; and therapeutic efficacy. Overall, the completely noninvasive and patient-friendly nature of the urine-based biopsy warrants further development and offers a promising alternative to blood-based biopsies.

Keywords: cancer; liquid biopsy; nonurological; urine.

FIG. 1.

Characterization of urine DNA. (A) DNA isolated from urine of five individuals. Fifteen milliliters of urine was collected from five volunteers. DNA was isolated and analyzed in an 8% polyacrylamide gel. The gel was stained with ethidium bromide and photographed. The first and the last lanes labeled “M” are two different DNA molecular weight markers. The high (H) and low (L) MW urine DNA is indicated. (B) Urine contains both HMW and LMW DNA. DNA isolated from one volunteer was aliquoted. Each aliquot was digested with RNase A, DNase I, or left untreated, and analyzed. (C) LMW urine DNA co-migrates with 1–2 nucleosomal-sized DNA from serum. DNA isolated from 15 mL of urine (U) from a volunteer, and 4 mL of human serum (Sigma) (S) was analyzed. Expected mobilities of 1 to 2 unit sizes of nucleosomal (mononucleosomal (mo) and dinucleosomal (di)) DNA fragments are indicated. (D) Recovery of HMW DNA from cell debris associated fraction and LMW DNA from cell-free supernatant fraction. Recovery of LMW urine DNA (L) in the supernatant of urine. DNA recovered from the total urine (T), the supernatant (Sup), and the cell debris pellet (C). Reprinted from Su et al. (2005), Copyright (2005), with permission from IOS Press. Reprinted from Su et al. (2004b), Copyright (2004), with permission from Elsevier. HMW, high molecular weight; LMW, low molecular weight.