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Updated: May 4, 2026
MicroRNA Based Liquid Biopsy: The Experience of the Plasma miRNA Signature Classifier MSC for Lung Cancer Screening
Published on: October 26, 2017
Clinical utility of a plasma-based miRNA signature classifier within computed tomography lung cancer screening: a
Gabriella Sozzi1, Mattia Boeri, Marta Rossi
1Gabriella Sozzi, Mattia Boeri, Carla Verri, Paola Suatoni, Luca Roz, Davide Conte, Michela Grassi, Tumor Genomics Unit; Ugo Pastorino, Thoracic Surgery Unit; Alfonso Marchiano, Radiology Unit, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale dei Tumori; Marta Rossi, Francesca Bravi, Eva Negri, Carlo La Vecchia, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri"; Francesca Bravi and Carlo La Vecchia, University of Milan, Milan; and Nicola Sverzellati, University of Parma, Parma, Italy.
Purpose:
Recent screening trial results indicate that low-dose computed tomography (LDCT) reduces lung cancer mortality in high-risk patients. However, high false-positive rates, costs, and potential harms highlight the need for complementary biomarkers. The diagnostic performance of a noninvasive plasma microRNA signature classifier (MSC) was retrospectively evaluated in samples prospectively collected from smokers within the randomized Multicenter Italian Lung Detection (MILD) trial.
Patients And Methods:
Plasma samples from 939 participants, including 69 patients with lung cancer and 870 disease-free individuals (n = 652, LDCT arm; n = 287, observation arm) were analyzed by using a quantitative reverse transcriptase polymerase chain reaction-based assay for MSC. Diagnostic performance of MSC was evaluated in a blinded validation study that used prespecified risk groups.
Results:
The diagnostic performance of MSC for lung cancer detection was 87% for sensitivity and 81% for specificity across both arms, and 88% and 80%, respectively, in the LDCT arm. For all patients, MSC had a negative predictive value of 99% and 99.86% for detection and death as a result of disease, respectively. LDCT had sensitivity of 79% and specificity of 81% with a false-positive rate of 19.4%. Diagnostic performance of MSC was confirmed by time dependency analysis. Combination of both MSC and LDCT resulted in a five-fold reduction of LDCT false-positive rate to 3.7%. MSC risk groups were significantly associated with survival (χ1(2) = 49.53; P < .001).
Conclusion:
This large validation study indicates that MSC has predictive, diagnostic, and prognostic value and could reduce the false-positive rate of LDCT, thus improving the efficacy of lung cancer screening.
