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

2015; Impact Journals LLC; Volume: 6; Issue: 32 Linguagem: Inglês

10.18632/oncotarget.5210

1949-2553

Stefano Sestini, Mattia Boeri, Alfonso Marchianò, Giuseppe Pelosi, Carlotta Galeone, Carla Verri, Paola Suatoni, Nicola Sverzellati, Carlo La Vecchia, Gabriella Sozzi, Ugo Pastorino,

Radiomics and Machine Learning in Medical Imaging

// Stefano Sestini 1, * , Mattia Boeri 2, * , Alfonso Marchiano 3 , Giuseppe Pelosi 4, 5 , Carlotta Galeone 6 , Carla Verri 2 , Paola Suatoni 1 , Nicola Sverzellati 7 , Carlo La Vecchia 8, * , Gabriella Sozzi 2, * , Ugo Pastorino 1, * 1 Unit of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy 2 Unit of Tumor Genomics, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy 3 Unit of Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy 4 Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy 5 Department of Clinical and Biomedical Sciences Luigi Sacco, University of Milan, Milan, Italy 6 Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, Laboratory of Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy 7 Department of Clinical Sciences, Section of Radiology, University of Parma, Milan, Italy 8 Department 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.