Non-coding RNAs as prognostic biomarkers: A mirna signature specific for aggressive early-stage lung adenocarcinomas

Elisa Dama, Valentina Melocchi, Francesco Mazzarelli, Tommaso Colangelo, Roberto Cuttano, Leonarda Di Candia, Gian Maria Ferretti, Marco Taurchini, Paolo Graziano, Fabrizio Bianchi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number48
Pages (from-to)1-13
Number of pages13
JournalNon-coding RNA
Volume6
Issue number4
DOIs
Publication statusPublished - 2020

Keywords

  • Biomarkers
  • Gene expression
  • Lung cancer
  • MicroRNA
  • Prognosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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