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MicroRNA Based Liquid Biopsy: The Experience of the Plasma miRNA Signature Classifier (MSC) for Lung Cancer Screening
Published on: October 26, 2017
Liquid biopsy miRNA risk score in bladder cancer: Translational insights from patient-derived xenografts to
Maria-Alexandra Papadimitriou1, Katerina-Marina Pilala1, Konstantina Panoutsopoulou1
1Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
Background:
Bladder cancer (BlCa) surveillance requires lifelong invasive monitoring, imposing substantial patient burden and healthcare costs. This underscores the need for minimally-invasive precision medicine approaches. Herein, we investigated the circulating miRNome of BlCa patients to assess its clinical and translational utility.
Methods:
miRNA-seq was performed on tumors and matched plasma samples from 15 patient-derived xenograft (PDX) mouse models. The screening cohort of the study consisted of 216 patients, and circulating miRNAs were quantified by RT-qPCR following 3'-end poly(A)-tailing. Cox regression models were used to develop liquid biopsy-based miRNA risk-scores (miRisk-scores), for non-muscle invasive (NMIBC) and muscle invasive BlCa (MIBC).
Results:
miRNA-seq identified six miRNAs (miR-100, miR-1246, miR-1290, miR-193b, miR-375, miR-4488) that were concurrently upregulated in tumors and plasma, and correlated with advanced stage/grade and early progression in PDX mouse models. In our screening cohort, elevated miR-375 and miR-4488 were associated with poorer NMIBC prognosis, whereas miR-1290 and miR-193b with worse survival in MIBC. Higher miRisk-scores were associated with short-term relapse and progression in NMIBC, while miRisk score-fitted multivariate models improved TaT1 risk-stratification. Moreover, higher miRisk-scores correlated with worse clinical outcomes in MIBC, and enhanced the prognostic performance of clinical markers.
Conclusion:
Overall, liquid biopsy miRNA signatures offer a minimally-invasive tool to complement biopsy-based assessments and refine BlCa risk-stratification and prognosis.