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Article

Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas

1
Cancer Biomarkers Unit, Fondazione IRCCS Casa Sollievo Della Sofferenza, 71013 San Giovanni Rotondo (FG), Italy
2
Pathology Unit, Fondazione IRCCS Casa Sollievo Della Sofferenza, 71013 San Giovanni Rotondo (FG), Italy
3
Thoracic-Surgery Unit, Fondazione IRCCS Casa Sollievo Della Sofferenza, 71013 San Giovanni Rotondo (FG), Italy
*
Author to whom correspondence should be addressed.
These authors have contributed equally.
Received: 30 October 2020 / Revised: 9 December 2020 / Accepted: 11 December 2020 / Published: 15 December 2020
(This article belongs to the Collection Feature Papers in Non-coding RNA)
Lung cancer burden can be reduced by adopting primary and secondary prevention strategies such as anti-smoking campaigns and low-dose CT screening for high risk subjects (aged >50 and smokers >30 packs/year). Recent CT screening trials demonstrated a stage-shift towards earlier stage lung cancer and reduction of mortality (~20%). However, a sizable fraction of patients (30–50%) with early stage disease still experience relapse and an adverse prognosis. Thus, the identification of effective prognostic biomarkers in stage I lung cancer is nowadays paramount. Here, we applied a multi-tiered approach relying on coupled RNA-seq and miRNA-seq data analysis of a large cohort of lung cancer patients (TCGA-LUAD, n = 510), which enabled us to identify prognostic miRNA signatures in stage I lung adenocarcinoma. Such signatures showed high accuracy (AUC ranging between 0.79 and 0.85) in scoring aggressive disease. Importantly, using a network-based approach we rewired miRNA-mRNA regulatory networks, identifying a minimal signature of 7 miRNAs, which was validated in a cohort of FFPE lung adenocarcinoma samples (CSS, n = 44) and controls a variety of genes overlapping with cancer relevant pathways. Our results further demonstrate the reliability of miRNA-based biomarkers for lung cancer prognostication and make a step forward to the application of miRNA biomarkers in the clinical routine. View Full-Text
Keywords: lung cancer; microRNA; gene expression; biomarkers; prognosis lung cancer; microRNA; gene expression; biomarkers; prognosis
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MDPI and ACS Style

Dama, E.; Melocchi, V.; Mazzarelli, F.; Colangelo, T.; Cuttano, R.; Di Candia, L.; Ferretti, G.M.; Taurchini, M.; Graziano, P.; Bianchi, F. Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas. Non-Coding RNA 2020, 6, 48. https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6040048

AMA Style

Dama E, Melocchi V, Mazzarelli F, Colangelo T, Cuttano R, Di Candia L, Ferretti GM, Taurchini M, Graziano P, Bianchi F. Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas. Non-Coding RNA. 2020; 6(4):48. https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6040048

Chicago/Turabian Style

Dama, Elisa, Valentina Melocchi, Francesco Mazzarelli, Tommaso Colangelo, Roberto Cuttano, Leonarda Di Candia, Gian M. Ferretti, Marco Taurchini, Paolo Graziano, and Fabrizio Bianchi. 2020. "Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas" Non-Coding RNA 6, no. 4: 48. https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6040048

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