Baseline computed tomography screening and blood microRNA predict lung cancer risk and define adequate intervals in the BioMILD trial

Abstract

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A Cross-Comparison of High-Throughput Platforms for Circulating MicroRNA Quantification, Agreement in Risk Classification, and Biomarker Discovery in Non-Small Cell Lung Cancer

“…Blood was collected from stage IV NSCLC patients and heavy smoker healthy individuals, as controls, with no history of cancer or other diseases. Patients and controls were classified, according to their class of risk, based on the reference MSC test generated from the ratios of 24 plasma miRs (12)(13)(14). The test was performed, as previously described, using a Custom RT and Pre-amplification Pools with TaqMan MiR Assays (Thermo Fisher Scientific, Waltham, MA, USA) (12)(13)(14).…”

“…Patients and controls were classified, according to their class of risk, based on the reference MSC test generated from the ratios of 24 plasma miRs (12)(13)(14). The test was performed, as previously described, using a Custom RT and Pre-amplification Pools with TaqMan MiR Assays (Thermo Fisher Scientific, Waltham, MA, USA) (12)(13)(14). The clinical characteristics and MSC scores of the participants to the study are listed in Table 1.…”

“…Circulating miRs (ct-miRs) are either stored in particles (exosomes, microvesicles, and apoptotic bodies) or associated with RNA-binding proteins or lipoproteins, which prevent their degradation (3)(4)(5). The stability, abundance, and variety of ct-miRs made them attractive candidates as non-invasive biomarkers for diagnosing, predicting, and monitoring diseases like cancer (6)(7)(8), and increasing attention is being paid to their role in lung carcinogenesis (9)(10)(11)(12)(13)(14)(15)(16).…”

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“…In our institution, the use of ct-miRs for the early detection of lung cancer has been assessed as a complementary diagnostic tool in the context of low-dose computed tomography (LDCT) screening in large retrospective cohorts (12,13). These studies led to the development of a plasma miR signature classifier (MSC) based on reciprocal ratios of 24 plasma miRs able to stratify individuals undergoing lung cancer screening into three levels (high, intermediate, and low) according to the risk of developing lethal lung cancer (13,14). As assessed in samples collected from smokers within the randomized Multicenter Italian Lung Detection trial, a large retrospective validation study, MSC resulted in a sensitivity, specificity, positive predicted value, and negative predictive value of 87, 81, 27, and 99% (13).…”

“…As assessed in samples collected from smokers within the randomized Multicenter Italian Lung Detection trial, a large retrospective validation study, MSC resulted in a sensitivity, specificity, positive predicted value, and negative predictive value of 87, 81, 27, and 99% (13). The utility of the classifier was also recently assessed, thanks to the prospective BioMILD screening trial on 4,119 high-risk volunteers, where MSC-positive participants had a 2-fold higher risk to develop lung cancer within the fourth year of screening than MSC-negative participants, independently of the low-dose computed tomography (LDCT) result (14). The risk level given by MSC reflects microenvironment-related changes associated to lung cancer development and aggressiveness.…”