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Spagnuolo, Manuela; Costantini, Manuela; Ferriero, Mariaconsiglia; Varmi, Marco; Sperduti, Isabella; Regazzo, Giulia; Cicchillitti, Lucia; Díaz Méndez, Ana Belén; Cigliana, Giovanni; Pompeo, Vincenzo; Russo, Andrea; Laquintana, Valentina; Mastroianni, Riccardo; Piaggio, Giulia; Anceschi, Umberto; Brassetti, Aldo; Bove, Alfredo; Tuderti, Gabriele; Flammia, Rocco Simone; Gallucci, Michele; Simone, Giuseppe; Rizzo, Maria Giulia
Journal of experimental & clinical cancer research, 04/2020, Letnik: 39, Številka: 1Journal Article
High grade non-muscle-invasive bladder cancer (HG-NMIBC) is a heterogeneous disease with variable risk of progression. Urinary microRNAs are promising biomarkers for BC detection and surveillance. Let-7c-5p miRNA, clustered with miR-99a-5p and -125b-5p, is deregulated in cancer, including BC. The aim of this study is to evaluate urinary let-7c cluster expression in Ta/T1 HG-NMIBC patients and its impact on progression-free survival (PFS). Quantitative Real-Time-Polymerase-Chain-Reaction (qRT-PCR) was used to analyze the let-7c cluster expression in 57 urine and 49 neoplastic paired tissue samples prospectively collected from transurethral resection (TUR) HG-NMIBC patients. Twenty urine and 10 bladder tissue samples were collected and analyzed as normal controls. QRT-PCR was also used to detect intra-/extra-cellular let-7c cluster in BC cells. Receiver Operating Characteristic (ROC) curves were used to identify urinary miRNAs cut-off values predicting T-stage and PFS. Uni/multivariable Cox regression was performed to identify predictors of PFS. A nomogram predicting progression risk and a decision curve analysis (DCA) were performed. Urinary let-7c was significantly up-regulated in patients compared with controls, while the whole cluster was down-regulated in tumor tissues. Supporting these findings, in vitro comparison of extra-/intra-cellular ratios of cluster levels between BC cells, showed a higher ratio for let-7c in HG-NMIBC versus low-grade cells. Urinary let-7c cluster expression was increased in higher T-stage and was an independent predictor of progression. Lower EORTC-score and downregulation of urinary cluster were predictors of higher PFS on univariable Cox regression, while on multivariable analysis only cluster expression was an independent progression predictor. On DCA, a benefit was evident for patients with a PFS probability > 20%. Urinary let-7c cluster evaluation may improve prognosis, identifying patients at risk of progression and addressing early radical treatment.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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