Accurate Diagnosis of High-Risk Pulmonary Nodules Using a Non-Invasive Epigenetic Biomarker Test
Journal
Cancers
Series/Report No.
Cancers
Journal Volume
17
Journal Issue
6
Start Page
916
ISSN
2072-6694
Date Issued
2025-03-07
Author(s)
Lu, Tzu-Pin
Lu, Hsiao-Hung
Pamart, Dorian
Kotronoulas, Aristotelis
Herzog, Marielle
Micallef, Jacob Vincent
Abstract
Background/objectives: Accurate non-invasive tests to improve early detection and diagnosis of lung cancer are urgently needed. However, no regulatory-approved blood tests are available for this purpose. We aimed to improve pulmonary nodule classification to identify malignant nodules in a high-prevalence patient group.
Methods: This study involved 806 participants with undiagnosed nodules larger than 5 mm, focusing on assessing nucleosome levels and histone modifications (H3.1 and H3K27Me3) in circulating blood. Nodules were classified as malignant or benign. For model development, the data were randomly divided into training (n = 483) and validation (n = 121) datasets. The model's performance was then evaluated using a separate testing dataset (n = 202).
Results: Among the patients, 755 (93.7%) had a tissue diagnosis. The overall malignancy rate was 80.4%. For all datasets, the areas under curves were as follows: training, 0.74; validation, 0.86; and test, 0.79 (accuracy range: 0.80-0.88). Sensitivity showed consistent results across all datasets (0.91, 0.95, and 0.93, respectively), whereas specificity ranged from 0.37 to 0.64. For smaller nodules (5-10 mm), the model recorded accuracy values of 0.76, 0.88, and 0.85. The sensitivity values of 0.91, 1.00, and 0.94 further highlight the robust diagnostic capability of the model. The performance of the model across the reporting and data system (RADS) categories demonstrated consistent accuracy.
Conclusions: Our epigenetic biomarker panel detected non-small-cell lung cancer early in a high-risk patient group with high sensitivity and accuracy. The epigenetic biomarker model was particularly effective in identifying high-risk lung nodules, including small, part-solid, and non-solid nodules, and provided further evidence for validation.
Subjects
circulating nucleosomes
epigenetic biomarkers
histone PTMs
liquid biopsy
lung cancer
pulmonary nodule
Publisher
MDPI AG
Type
journal article