Bladder cancer (BC) is the most frequent malignancy of the urinary tract with a high incidence in men and smokers. Currently, there are no non-invasive markers useful for BC diagnosis and subtypes classification that could overcome invasive procedures such as cystoscopy. Dysregulated miRNA profiles have been associated with numerous cancers, including BC. Cell-free miRNAs are abundantly present in a variety of biofluids including urine and make them promising candidates in cancer biomarker discovery. In the present study, the identification of miRNA fingerprints associated with different BC status was performed by next-generation sequencing on urine samples from 66 BC and 48 controls. Three signatures based on dysregulated miRNAs have been identified by regression models, assessing the power to discriminate different BC subtypes. Altered miRNAs according to invasiveness and grade were validated by qPCR on 112 cases and 65 controls (among which 46 cases and 16 controls were an independent group of subjects while the rest were replica samples). The area under the curve (AUC) computed including three miRNAs (miR-30a-5p, let-7c-5p and miR-486-5p) altered in all BC subtypes showed a significantly increased accuracy in the discrimination of cases and controls (AUC model = 0.70; p-value = 0.01). In conclusions, the non-invasive detection in urine of a selected number of miRNAs altered in different BC subtypes could lead to an accurate early diagnosis of cancer and stratification of patients.

microRNA profiles in urine by next-generation sequencing can stratify bladder cancer subtypes

Pardini Barbara
Co-first
;
Cordero Francesca
Co-first
;
Viberti Clara;Birolo Giovanni;Oderda Marco;Di Gaetano Cornelia;Arigoni Maddalena;Martina Federica;Calogero Raffaele;Sacerdote Carlotta;Gontero Paolo;Vineis Paolo;Matullo Giuseppe
Last
2018-01-01

Abstract

Bladder cancer (BC) is the most frequent malignancy of the urinary tract with a high incidence in men and smokers. Currently, there are no non-invasive markers useful for BC diagnosis and subtypes classification that could overcome invasive procedures such as cystoscopy. Dysregulated miRNA profiles have been associated with numerous cancers, including BC. Cell-free miRNAs are abundantly present in a variety of biofluids including urine and make them promising candidates in cancer biomarker discovery. In the present study, the identification of miRNA fingerprints associated with different BC status was performed by next-generation sequencing on urine samples from 66 BC and 48 controls. Three signatures based on dysregulated miRNAs have been identified by regression models, assessing the power to discriminate different BC subtypes. Altered miRNAs according to invasiveness and grade were validated by qPCR on 112 cases and 65 controls (among which 46 cases and 16 controls were an independent group of subjects while the rest were replica samples). The area under the curve (AUC) computed including three miRNAs (miR-30a-5p, let-7c-5p and miR-486-5p) altered in all BC subtypes showed a significantly increased accuracy in the discrimination of cases and controls (AUC model = 0.70; p-value = 0.01). In conclusions, the non-invasive detection in urine of a selected number of miRNAs altered in different BC subtypes could lead to an accurate early diagnosis of cancer and stratification of patients.
2018
9
20658
20669
Pardini Barbara, Cordero Francesca, Naccarati Alessio, Viberti Clara, Birolo Giovanni, Oderda Marco, Di Gaetano Cornelia, Arigoni Maddalena, Martina Federica, Calogero Raffaele, Sacerdote Carlotta, Gontero Paolo, Vineis Paolo, Matullo Giuseppe
File in questo prodotto:
File Dimensione Formato  
oncotarget-09-20658.pdf

Accesso aperto

Tipo di file: PDF EDITORIALE
Dimensione 1.23 MB
Formato Adobe PDF
1.23 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1662870
Citazioni
  • ???jsp.display-item.citation.pmc??? 39
  • Scopus 58
  • ???jsp.display-item.citation.isi??? ND
social impact