Clinical utility of a plasma-based miRNA signature classifier within computed tomography lung cancer screening: a correlative MILD trial study

J Clin Oncol. 2014 Mar 10;32(8):768-73. doi: 10.1200/JCO.2013.50.4357. Epub 2014 Jan 13.

Abstract

Purpose: Recent screening trial results indicate that low-dose computed tomography (LDCT) reduces lung cancer mortality in high-risk patients. However, high false-positive rates, costs, and potential harms highlight the need for complementary biomarkers. The diagnostic performance of a noninvasive plasma microRNA signature classifier (MSC) was retrospectively evaluated in samples prospectively collected from smokers within the randomized Multicenter Italian Lung Detection (MILD) trial.

Patients and methods: Plasma samples from 939 participants, including 69 patients with lung cancer and 870 disease-free individuals (n = 652, LDCT arm; n = 287, observation arm) were analyzed by using a quantitative reverse transcriptase polymerase chain reaction-based assay for MSC. Diagnostic performance of MSC was evaluated in a blinded validation study that used prespecified risk groups.

Results: The diagnostic performance of MSC for lung cancer detection was 87% for sensitivity and 81% for specificity across both arms, and 88% and 80%, respectively, in the LDCT arm. For all patients, MSC had a negative predictive value of 99% and 99.86% for detection and death as a result of disease, respectively. LDCT had sensitivity of 79% and specificity of 81% with a false-positive rate of 19.4%. Diagnostic performance of MSC was confirmed by time dependency analysis. Combination of both MSC and LDCT resulted in a five-fold reduction of LDCT false-positive rate to 3.7%. MSC risk groups were significantly associated with survival (χ1(2) = 49.53; P < .001).

Conclusion: This large validation study indicates that MSC has predictive, diagnostic, and prognostic value and could reduce the false-positive rate of LDCT, thus improving the efficacy of lung cancer screening.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis*
  • Chi-Square Distribution
  • False Positive Reactions
  • Female
  • Gene Expression Profiling*
  • Genetic Testing / methods*
  • Humans
  • Italy / epidemiology
  • Kaplan-Meier Estimate
  • Lung Neoplasms / blood
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Mass Screening / methods*
  • MicroRNAs / blood*
  • Middle Aged
  • Multicenter Studies as Topic
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Reproducibility of Results
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Smoking / adverse effects
  • Smoking / mortality
  • Time Factors
  • Tomography, X-Ray Computed*

Substances

  • Biomarkers, Tumor
  • MicroRNAs