Validation of Lung EpiCheck, a novel methylation-based blood assay, for the detection of lung cancer in European and Chinese high-risk individuals

Abstract

AimLung cancer screening reduces mortality. We aim to validate the performance of Lung EpiCheck®, a 6-marker panel methylation-based plasma test, in the detection of lung cancer in European and Chinese samples.MethodsA case-control European training set (102 lung cancer cases/265 controls) was used to define the panel and algorithm. Two cut-offs were selected, low cut-off (LCO) for high sensitivity and high cut-off (HCO) for high specificity. The performance was validated in case-control European and Chinese validation sets (cases/controls: 179/137 and 30/15).ResultsThe European and Chinese validation sets achieved AUCs of 0.882 and 0.899, respectively. The respective sensitivity/specificity with LCO were 87.2%/64.2% and 76.7%/93.3% and with HCO were 74.3%/90.5% and 56.7%/100.0%, respectively. Stage I NSCLC sensitivity in European and Chinese samples with LCO was 78.4% and 70.0% and with HCO was 62.2% and 30.0%, respectively. SCLC was represented only in the European set and sensitivities with LCO and HCO were 100.0% and 93.3%. In multivariable analyses of the European validation set, the assay's ability to predict lung cancer was independent of established risk factors (age, smoking, COPD), and overall AUC was 0.942.ConclusionsLung EpiCheck demonstrated strong performance in lung cancer prediction in case-control European and Chinese samples, detecting high proportions of early stage NSCLC and SCLC and significantly improving predictive accuracy when added to established risk factors. Prospective studies are required to confirm these findings. Utilising such a simple and inexpensive blood test has the potential to improve compliance and broaden access to screening for at-risk populations.

Impact of Preanalytical and Analytical Methods on Cell-Free DNA Diagnostics

“…cfDNA methylation presents itself as a valuable biomarker in liquid biopsy research due to its high specificity for various biological states and robust biological stability ( Constâncio et al, 2020 ; Miller et al, 2021 ), with some authors even presenting cfDNA methylation status as the universal cancer biomarker ( Meddeb et al, 2019 ). Recent reports highlight multiple possible applications of the cfDNA methylation profiling among which are: being able to identify the tissue of origin and discern between different tissues (healthy and cancerous) ( Moss et al, 2018 ; Stewart et al, 2018 ; Gaga et al, 2020 ; Sprang et al, 2020 ; Miller et al, 2021 ), as well as guiding therapy selection and monitoring disease prognosis ( Somen et al, 2019 ; Tuaeva et al, 2019 ; Li S. et al, 2020 ). For example, LINE-1 cfDNA hypomethylation is associated with multiple cancer characteristics, such as risk, type, progression, and poor prognosis ( Lee et al, 2019 ).…”

Biomarkers in lung cancer screening: the importance of study design

“…The biomarker should then be compared with the gold-standard method for the clinical application of interest, for example, to risk prediction models if intended for use in defining eligibility for screening. Also in this issue of the ERJ, GAGA et al [15] report on a novel methylation-based biomarker, Lung EpiCheck, which shows a sensitivity of 85% for early stage lung cancer, with a specificity of 64% when combined with other risk factors. This new test is promising but, quite rightly, the authors recommend further prospective trials to establish how the test performs in populations eligible for screening.…”

DNA methylation analysis of tumor suppressor genes in liquid biopsy components of early stage NSCLC: a promising tool for early detection

“…Based on epigenetic alterations two commercially available tests for colorectal cancer and lung cancer detection in plasma-cfDNA levels namely “Epi proColon” (methylation in SEPT 9) and “Epi proLung” (methylation in PTGER4 and SHOX2 ), respectively, were used in clinical practice [ 16 ], [ 17 ]. Recently, a six-marker panel methylation-based plasma test, namely lung EpiCheck was validated for the detection of lung cancer [ 18 ].…”