Liquid Biopsy Landscape in Patients with Primary Upper Tract Urothelial Carcinoma

Abstract

Urothelial carcinomas (UCs) are a broad and heterogeneous group of malignancies, with the prevalence of upper tract urothelial carcinoma (UTUC) being rare, accounting for only 5–10% of total malignancies. There is a need for additional toolsets to assist the current clinical paradigm of care for patients with UTUC. As a non-invasive tool for the discovery of cancer-related biomarkers, the liquid biopsy has the potential to represent the complex process of tumorigenesis and metastasis. Herein, we show the efficacy of the liquid biopsy as a source of biomarkers for detecting UTUC. Using the third-generation high-definition single-cell assay (HDSCA3.0) workflow, we investigate liquid biopsy samples collected from patients with UTUC and normal donors (NDs) to provide critical information regarding the molecular and morphological characteristics of circulating rare events. We document several important findings from the liquid biopsy analysis of patients diagnosed with UTUC prior to surgery: (1) Large extracellular vesicles (LEVs) and circulating tumor cells (CTCs) are detectable in the peripheral blood. (2) The rare-event profile is highly heterogeneous. (3) Clinical data elements correlate with liquid biopsy analytes. Overall, this study provides evidence for the efficacy of the liquid biopsy in understanding the biology of UTUC with the future intent of informing clinical decision making, ultimately improving patient outcomes.

Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical Utility

“…Oncosomes comprised a significant portion of the rare-event profiles from both the CDX2-targeted and Landscape assays in mCRC patient samples. HDSCA has previously identified oncosomes with similar size and biomarker expression in prostate cancer [46], bladder cancer [48] and upper tract urothelial carcinoma [51], suggesting that these events may be found in a variety of cancer types. Most importantly, oncosome enumerations from both IF protocols correlated with PFS in this cohort.…”

“…Classifications were validated by multiple hematopathologist-trained technical analysts. Previously described as large extracellular vesicles in the context of HDSCA [46,48,51], oncosomes were identified as circular, DAPI-negative events with positive CK expression [44,52,53]. Initially presented as adjacent to nucleated common cells or as individual DAPI-negative events, oncosomes were manually classified and confirmed by trained analysts.…”

Modern Kidney-Sparing Management of Upper Tract Urothelial Carcinoma

“…The key step in KSS is appropriate patient selection, which highly relies on preoperative risk stratification to find low-risk cases. Novel diagnostic and prognostic tools, such as urine-based methylation and blood-based liquid biopsy biomarkers, can help in optimizing preoperative risk stratification and proper patient selection for KSS [ 64 , 65 ]. In addition, these novel markers can be beneficial in the surveillance setting of patients with UTUC undergoing KSS to avoid unnecessary procedures (e.g., URS).…”

PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial

“…We also evaluated treatment response by CTC quantification in the peripheral blood of treated participants on study using high-definition single-cell analysis (HDSCA) [11][12][13] . Cytokeratin (CK)-positive cells were detected in the peripheral blood of 100% of treated individuals.…”

“…CTCs were evaluated by the Convergent Science Institute in Cancer of the USC Michelson Center for Convergent Bioscience. In short, peripheral blood and bone marrow aspirate samples were collected and shipped to the laboratory for processing and plating onto glass slides before staining with an immunofluorescence assay and imaging via automated high-throughput fluorescence scanning microscopy at ×100 magnification [11][12][13]35 . Rare events (for example, CTCs) were detected and classified using a custom computational methodology as previously reported [11][12][13]35 .…”