miRNA as biomarkers for early lung cancer detection
1Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
Detection of lung cancer at an early stage offers the real potential to reduce mortality with new chances of cure. Although low-dose CT screening (LDCT) is currently the standard of care for early lung cancer detection, it results in a general over diagnosis of indolent nodules, thus increasing unnecessary confirmatory diagnostic procedures. Circulating microRNAs (miRNAs), represent promising complementary biomarkers since they act as extracellular messengers of biological signals derived from the cross-talk between the tumor and its surrounding microenvironment. We developed a miRNA signature classifier (MSC) containing 24 miRNAs and tested its performance in an enlarged validation set composed of 85 patients and 1000 controls belonging to the MILD trial [1,2]. The results of this study showed that the combination of MSC and LDCT reduced LDCT false-positive rate from 19.4% to 3.7% and that the MSC risk groups were significantly associated with survival. The diagnostic characteristic of MSC that showed high sensitivity (87%) and specificity (81%) coupled with an NPV of 99% indicates that MSC is a clinically useful screening test. Importantly, the diagnostic performance of MSC as a predictor of lung cancer development was confirmed by the time dependency analysis given the availability of pre-disease plasma samples. More recently, taking advantage of results obtained in two screening programs with a total follow up of 23,967 person-years and a median time follow-up of 5.9 years, we proved the prognostic value and the disease-monitoring capacity of MSC in lung cancer patients identified in LDCT screening programs (unpublished data).The results presented highlight the clinical usefulness of circulating miRNAs as predictive, diagnostic, prognostic and monitoring tool in lung cancer.
- 1. Boeri M, Verri C, Conte D et al. Proc Natl Acad Sci U S A 2011; 108:3713-8.
- 2. Sozzi G, Boeri M, Rossi M et al. J Clin Oncol 2014;32:768-73