School of Biomedical Engineering, Bio-ID Center, Shanghai Jiao Tong University, Shanghai 200240, China.
Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Lung Cancer Center, Shanghai Jiao Tong University, Shanghai 200030, China.
Dis Markers. 2022 Jan 27;2022:9619357. doi: 10.1155/2022/9619357. eCollection 2022.
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.
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.
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.
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.
肺癌是全球最常见的癌症之一。作为液体活检分析物之一，游离 DNA（cfDNA）甲基化的改变可以作为肺癌检测的有前途的生物标志物。
在这项研究中，进行了差异甲基化分析以鉴定候选标志物，并使用 10 倍交叉验证（CV）进行套索回归以建立诊断标志物组合。使用接收者操作特征（ROC）曲线和精度-召回（PR）曲线评估二分类器的性能。
我们根据 cfDNA 甲基化数据确定了 4072 个差异甲基化区域（DMR），然后建立了一个包含 10 个 DMR 的标志物组合。该组合在包含 29 个肺癌和 74 个正常样本的 cfDNA 队列中，ROC 曲线下面积（AUROC）为 0.922，PR 曲线下面积（AUPR）为 0.899，表现出色。此外，cfDNA 衍生的标志物在原发性组织数据集中也表现良好，比组织衍生的标志物更稳健。
我们的研究表明，该 10-DMR 标志物组合具有很高的准确性和稳健性，可能是肺癌检测的一种新的有前途的靶标。
