Circulating microRNA signature as liquid-biopsy to monitor lung cancer in low-dose computed tomography screening

Abstract

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Stefano Sestini1, *, Mattia Boeri2, *, Alfonso Marchiano3, Giuseppe Pelosi4, 5, Carlotta Galeone6, Carla Verri2, Paola Suatoni1, Nicola Sverzellati7, Carlo La Vecchia8, *, Gabriella Sozzi2, *, Ugo Pastorino1, * 1Unit of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy 2Unit of Tumor Genomics, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy 3Unit of Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy 4Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy 5Department of Clinical and Biomedical Sciences Luigi Sacco, University of Milan, Milan, Italy 6Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, Laboratory of Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy 7Department of Clinical Sciences, Section of Radiology, University of Parma, Milan, Italy 8Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy *These authors have contributed equally to this work Correspondence to: Ugo Pastorino, e-mail: ugo.pastorino@istitutotumori.mi.it Keywords: lung cancer, microRNA, liquid biopsy, LDCT screening, prognosis Received: July 02, 2015 Accepted: September 25, 2015 Published: October 06, 2015 ABSTRACT Liquid biopsies can detect biomarkers carrying information on the development and progression of cancer. We demonstrated that a 24 plasma-based microRNA signature classifier (MSC) was capable of increasing the specificity of low dose computed tomography (LDCT) in a lung cancer screening trial. In the present study, we tested the prognostic performance of MSC, and its ability to monitor disease status recurrence in LDCT screening-detected lung cancers. Between 2000 and 2010, 3411 heavy smokers enrolled in two screening programmes, underwent annual or biennial LDCT. During the first five years of screening, 84 lung cancer patients were classified according to one of the three MSC levels of risk: high, intermediate or low. Kaplan-Meier survival analysis was performed according to MSC and clinico-pathological information. Follow-up MSC analysis was performed on longitudinal plasma samples (n = 100) collected from 31 patients before and after surgical resection. Five-year survival was 88.9% for low risk, 79.5% for intermediate risk and 40.1% for high risk MSC (p = 0.001). The prognostic power of MSC persisted after adjusting for tumor stage (p = 0.02) and when the analysis was restricted to LDCT-detected cases after exclusion of interval cancers (p < 0.001). The MSC risk level decreased after surgery in 76% of the 25 high-intermediate subjects who remained disease free, whereas in relapsing patients an increase of the MSC risk level was observed at the time of detection of second primary tumor or metastatic progression. These results encourage exploiting the MSC test for lung cancer monitoring in LDCT screening for lung cancer.