NcRNA-based signatures as early detection biomarkers for non-small cell lung cancer

Keywords

ncRNA - early-detection - NSCLC - biomarkers - lung cancer screening

Lung cancer is the main cause of cancer-related deaths worldwide. The poor prognosis of lung cancer patients is due to diagnosis at advanced stages. The detection of biomarkers in body fluids, as liquid biopsy, may serve as a tool for risk assessment, with the potential to enhance early disease diagnosis. This project aimed to identify non-coding RNA (ncRNA)-based signatures for the early detection of non-small cell lung cancer (NSCLC) using liquid biopsies. This is a case-control study with subjects and patients from Barretos Cancer Hospital (n = 123) and Hospital Universitari Quiron Dexeus (n = 186). ncRNAs (miRNAs and circRNAs) were analyzed in plasma and/or sputum samples from non-metastatic NSCLC patients and controls. Expression analysis was conducted using NanoString Technologies™ assays: Human v3 miRNA assay (800 miRNAs) and Custom nCounter ElementsXT (74 circRNAs). Raw data were normalized by coeficient of variation (miRNA) or DeSeq/RUVSeq (circRNA) followed by diferential expression analysis filtered using RStudio (miRNA: binary logistic regression; circRNA: random forest). In plasma, we identified ten differentially expressed miRNAs (AUC=0.827; mean signature score: cases=3.9 vs. controls=1.8) distinguishing NSCLC patients from high-risk subjects. In sputum, we identified seven miRNAs (AUC=0.776; mean signature score: cases=3.8 vs. controls =5.3) for distinguishing cancer patients from control subjects. Both differentially expressed miRNAs sets were fluid-specific. For circRNAs, we identified four differentially expressed genes with high accuracy for distinguishing cancer patients from healthy subjects (AUC = 0.745). The presence of the 4-circRNA signature was exclusively associated with cancer status (OR=4.28). In conclusion, we identified ncRNA-based signatures in liquid biopsy samples that could potentially be employed for early detection of lung cancer including screening programs to improve the detection rates of early-stages lung cancer.

Corresponding author: Letícia Ferro Leal (e-mail: [e-mail]).