Characterization of Cellular and Acellular Analytes from Pre-Cystectomy Liquid Biopsies in Patients Newly Diagnosed with Primary Bladder Cancer.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI
    • Abstract:
      Urinary bladder cancer (BCa) is the 10th most frequent cancer in the world, most commonly found among the elderly population, and becomes highly lethal once cells have spread from the primary tumor to surrounding tissues and distant organs. Cystectomy, alone or with other treatments, is used to treat most BCa patients, as it offers the best chance of cure. However, even with curative intent, 29% of patients experience relapse of the cancer, 50% of which occur within the first year of surgery. This study aims to use the liquid biopsy to noninvasively detect disease and discover prognostic markers for disease progression. Using the third generation high-definition single cell assay (HDSCA3.0), 50 bladder cancer patient samples and 50 normal donor (ND) samples were analyzed for circulating rare events in the peripheral blood (PB), including circulating tumor cells (CTCs) and large extracellular vesicles (LEVs). Here, we show that (i) CTCs and LEVs are detected in the PB of BCa patients prior to cystectomy, (ii) there is a high heterogeneity of CTCs, and (iii) liquid biopsy analytes correlate with clinical data elements. We observed a significant difference in the incidence of rare cells and LEVs between BCa and ND samples (median of 74.61 cells/mL and 30.91 LEVs/mL vs. 34.46 cells/mL and 3.34 LEVs/mL, respectively). Furthermore, using classification models for the liquid biopsy data, we achieved a sensitivity of 78% and specificity of 92% for the identification of BCa patient samples. Taken together, these data support the clinical utility of the liquid biopsy in detecting BCa, as well as the potential for predicting cancer recurrence and survival post-cystectomy to better inform treatment decisions in BCa care.
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    • Grant Information:
      KL2 TR001854 United States TR NCATS NIH HHS; Challenge Award Prostate Cancer Foundation; P01CA093900 United States CA NCI NIH HHS; KL2TR001854 United States TR NCATS NIH HHS; U01CA196390 United States CA NCI NIH HHS; 5P30CA014089-40 NCI's USC Norris Comprehensive Cancer Center (CORE)
    • Contributed Indexing:
      Keywords: HDSCA; bladder cancer; circulating tumor cell; cystectomy; large extracellular vesicle; liquid biopsy; peripheral blood; urothelial carcinoma
    • Publication Date:
      Date Created: 20220215 Latest Revision: 20240822
    • Publication Date:
      20240822
    • Accession Number:
      PMC8833768
    • Accession Number:
      10.3390/cancers14030758
    • Accession Number:
      35159025