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

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.

Mitochondrial microRNAs Are Dysregulated in Patients with Fabry Disease

“…We and others have shown that microRNAs (miRNAs), small non-coding RNAs of ~22 nucleotides, may serve as reliable biomarkers of various human disorders (Keller et al, 2014;Santulli et al, 2014;Sardu et al, 2014;Novak et al, 2015;Santulli, 2015;Santulli, 2016;Cammarata et al, 2018;Slota and Booth, 2019;Dama et al, 2020;Donati et al, 2021;Jankauskas et al, 2021;Kanach et al, 2021;Kansakar et al, 2022). Therefore, the microRNAs profile could be a promising biomarker candidate…”

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells

“…MicroRNAs (miRNAs, miRs) are small non-coding RNAs involved in post-transcriptional gene regulation [9][10][11][12]. They play crucial regulatory roles in a number of biological processes [13][14][15][16][17][18][19][20]. Of note, miRNAs represent a very attractive therapeutic strategy to manipulate various processes as their activity can be efficiently modulated with innovative and personalized technologies [21,22].…”

Comparative Analysis of Free-Circulating and Vesicle-Associated Plasma microRNAs of Healthy Controls and Early-Stage Lung Cancer Patients

“…Interestingly, comparative analysis against healthy subjects highlighted the presence of some specific miRNAs predominantly found in NSCLC patients in both FC and EV fractions. In particular, 8 miRNAs out of the 16 top-ranking miRNAs, which were enriched in patients’ EVs (mir-425-3p, mir-30b-5p, mir-181a-2-3p, mir-93-3p, miR-139-5p, miR-339-3p, miR-339-5p, and hsa-miR-196b-5p), in addition to 2 miRNAs out of the 19 top upregulated FC miRNAs (miR-331-3p and let-7f) are well known biomarkers associated with lung cancer [ 33 , 34 , 35 , 36 , 37 , 38 , 39 ].…”