title: Circulating microRNA signature as liquid-biopsy to monitor lung cancer in low-dose computed tomography screening.
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.
authors.affiliation: Unit of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sestini
authors.affiliation: Unit of Tumor Genomics, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Boeri
authors.affiliation: Unit of Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Marchiano
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.|Department of Clinical and Biomedical Sciences Luigi Sacco, University of Milan, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pelosi
authors.affiliation: 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.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Galeone
authors.affiliation: Unit of Tumor Genomics, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Verri
authors.affiliation: Unit of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Suatoni
authors.affiliation: Department of Clinical Sciences, Section of Radiology, University of Parma, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Sverzellati
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: La Vecchia
authors.affiliation: Unit of Tumor Genomics, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sozzi
authors.affiliation: Unit of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Pastorino
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D001706:Biopsy; D016009:Chi-Square Distribution; D018450:Disease Progression; D018572:Disease-Free Survival; D055088:Early Detection of Cancer / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D010865:Pilot Projects; D011013:Pneumonectomy; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011829:Radiation Dosage; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: LDCT screening; liquid biopsy; lung cancer; microRNA; prognosis