WCLC 2025 - Posters & ePosters-P1.04.45 Multi-Center Validation of a Circulating 9-microRNA Signature for Lung Cancer Early Detection

Pdf Summary

This study led by Dr. Fabrizio Bianchi validated a circulating 9-microRNA (miRNA) signature for early lung cancer (LC) detection in multi-center low-dose computed tomography (LD-CT) screening cohorts in Europe. Although LD-CT reduces lung cancer mortality by 20–30%, issues with cost, radiation exposure, false positives, and overdiagnosis persist. Blood-based miRNA biomarkers could improve specificity and reduce false positives, but previous signatures lacked extensive multi-cohort validation.<br /><br />The researchers conducted a multi-step methodology: an in-silico meta-analysis of 3 public circulating miRNA datasets identified differentially expressed miRNAs between LC patients and controls. Retrospective plasma samples from two Italian hospitals were pooled and profiled by qRT-PCR arrays, refining the candidate miRNAs. Intracellular expression was confirmed in 173 LC cell lines. Finally, diagnostic performance was tested in real-world LD-CT screening cohorts from Poland (MOLTEST-BIS trial) and Italy (SMAC-1 trial) including 72 screen-detected LC cases and 261 controls at high LC risk.<br /><br />A robust 9-miRNA signature was identified, showing strong diagnostic accuracy: area under curve (AUC) values of 0.78 (Polish cohort) and 0.75 (Italian cohort), with sensitivities of 76–82%, specificities of 67–68%, and overall accuracies ~70%. This signature’s performance was independent of tumor subtype, age, gender, smoking habits, and nodule characteristics. Importantly, it showed good detection of stage I lung cancer (AUC 0.69–0.76) and satisfactory discrimination of benign nodules (AUC 0.71).<br /><br />The study highlights the promise of this 9-miRNA circulating signature to complement LD-CT screening, enhancing early lung cancer detection accuracy across diverse populations and clinical settings. Ongoing research is exploring its utility for evaluating indeterminate lung nodules. This multi-center validation supports the signature’s potential clinical application to reduce false positives and improve lung cancer screening effectiveness.

Asset Subtitle

Fabrizio Bianchi

Meta Tag

Speaker Fabrizio Bianchi

Topic Screening and Early Detection

Keywords

lung cancer

microRNA signature

early detection

low-dose computed tomography

LD-CT screening

circulating biomarkers

multi-center validation

diagnostic accuracy

false positives reduction

stage I lung cancer