Abstract
Background Lung cancer is one of the most commonly diagnosed cancer worldwide. As one of the liquid biopsy analytes, alternations in cell-free DNA (cfDNA) methylation could function as promising biomarkers for lung cancer detection. Methods In this study, differential methylation analysis was performed to identify candidate markers, and lasso regression with 10-fold cross-validation (CV) was used to establish the diagnostic marker panel. The performance of the binary classifier was evaluated using the receiver operating characteristic (ROC) curve and the precision-recall (PR) curve. Results We identified 4072 differentially methylated regions (DMRs) based on cfDNA methylation data, and then a 10-DMR marker panel was established. The panel achieved an area under the ROC curve (AUROC) of 0.922 and an area under the PR curve (AUPR) of 0.899 in a cfDNA cohort containing 29 lung cancer and 74 normal samples, showing outstanding performance. Besides, the cfDNA-derived markers also performed well in primary tissue datasets, which were more robust than the tissue-derived markers. Conclusion Our study suggested that the 10-DMR marker panel attained high accuracy and robustness and may function as a novel and promising target for lung cancer detection.
Highlights
Lung cancer is one of the leading causes of cancer death in the world [1]
Four independent datasets were included in the study, among which cell-free DNA (cfDNA) and tissue sets 1 were for differential methylation analysis and cfDNA and tissue sets 2 were for model construction
Considering that representation bisulfite sequencing (RRBS) usually did not interrogate the same CpG loci as 450 k and EPIC array did, genomic coverage analysis was performed to test the concordance between the datasets using different detection techniques. 3 normal and 3 lung cancer samples in cfDNA set 2 were selected randomly to be examined in detail
Summary
Tissue biopsy is by far the gold standard to establish a diagnosis of cancer. Compared to tissue-based approaches, liquid biopsy, which analyzes circulating tumor markers from peripheral blood, is noninvasive and has less difficulty in obtaining samples [3]. Cell-free DNA (cfDNA), one of the liquid biopsy analytes, refers to extracellular DNA fragments mainly released from cells through apoptosis and necrosis [2]. Raised cfDNA levels in plasma were found in patients with cancer compared to healthy individuals [5]. The quantitative and genomic information of cfDNA allows for detecting cancer and monitoring disease burden. Lung cancer is one of the most commonly diagnosed cancer worldwide. As one of the liquid biopsy analytes, alternations in cell-free DNA (cfDNA) methylation could function as promising biomarkers for lung cancer detection
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
