Analysis of copy number alterations in bladder cancer stem cells revealed a prognostic role of LRP1B.

Autor: Conconi D; School of Medicine and Surgery, University of Milano-Bicocca, Monza, 20900, Italy. donatella.conconi@unimib.it., Jemma A; School of Medicine and Surgery, University of Milano-Bicocca, Monza, 20900, Italy., Giambra M; School of Medicine and Surgery, University of Milano-Bicocca, Monza, 20900, Italy.; PhD Program in Neuroscience, University of Milano-Bicocca, Monza, 20900, Italy., Redaelli S; School of Medicine and Surgery, University of Milano-Bicocca, Monza, 20900, Italy., Croci GA; Pathology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, 20122, Italy., Dalprà L; School of Medicine and Surgery, University of Milano-Bicocca, Monza, 20900, Italy., Lavitrano M; School of Medicine and Surgery, University of Milano-Bicocca, Monza, 20900, Italy., Bentivegna A; School of Medicine and Surgery, University of Milano-Bicocca, Monza, 20900, Italy. angela.bentivegna@unimib.it.
Jazyk: angličtina
Zdroj: World journal of urology [World J Urol] 2022 Sep; Vol. 40 (9), pp. 2267-2273. Date of Electronic Publication: 2022 Jul 16.
DOI: 10.1007/s00345-022-04093-1
Abstrakt: Purpose: Bladder cancer is the most common malignancy of the urinary tract and one of the most prevalent cancers worldwide. It represents a spectrum of diseases, from recurrent non-invasive tumors (NMIBCs) managed chronically, to muscle infiltrating and advanced-stage disease (MIBC) that requires multimodal and invasive treatment. Multiple studies have underlined the complexity of bladder tumors genome, highlighting many specific genetic lesions and genome-wide occurrences of copy-number alterations (CNAs). In this study, we analyzed CNAs of selected genes in our cohorts of cancer stem cells (CSCs) and in The Cancer Genome Atlas (TCGA-BLCA) cohort with the aim to correlate their frequency with patients' prognosis.
Methods: CNAs have been verified on our array-CGH data previously reported on 19 bladder cancer biopsies (10 NMIBCs and 9 MIBCs) and 16 matched isolated CSC cultures. In addition, CNAs data have been consulted on the TCGA database, to search correlations with patients' follow-up. Finally, mRNA expression levels of LRP1B in TGCA cohort were obtained from The Human Protein Atlas.
Results: We firstly identified CNAs differentially represented between TGCA data and CSCs derived from NMIBCs and MIBCs, and we correlated the presence of these CNAs with patients' follow-up. LRP1B loss was significantly increased in CSCs and linked to short-term poor prognosis, both at genomic and transcriptomic level, confirming its pivotal role in bladder cancer tumorigenesis.
Conclusion: Our study allowed us to identify potential "predictive" prognostic CNAs for bladder cancer, implementing knowledge for the ultimate goal of personalized medicine.
(© 2022. The Author(s).)
Databáze: MEDLINE
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