In Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Addressing the high false-positive rate of conventional low-dose computed tomography (LDCT) for lung cancer diagnosis, the efficacy of incorporating blood-based noninvasive testing for assisting practicing clinician's decision making in diagnosis of pulmonary nodules (PNs) is investigated. In this prospective observative study, next generation sequencing- (NGS-) based cell-free DNA (cfDNA) mutation profiling, NGS-based cfDNA methylation profiling, and blood-based protein cancer biomarker testing are performed for patients with PNs, who are diagnosed as high-risk patients through LDCT and subsequently undergo surgical resections, with tissue sections pathologically examined and classified. Using pathological classification as the gold standard, statistical and machine learning methods are used to select molecular markers associated with tissue's malignant classification based on a 98-patient discovery cohort (28 benign and 70 malignant), and to construct an integrative multianalytical model for tissue malignancy prediction. Predictive models based on individual testing platforms have shown varying levels of performance, while their final integrative model produces an area under the receiver operating characteristic curve (AUC) of 0.85. The model's performance is further confirmed on a 29-patient independent validation cohort (14 benign and 15 malignant, with power > 0.90), reproducing AUC of 0.86, which translates to an overall sensitivity of 80% and specificity of 85.7%.
Liu Quan-Xing, Zhou Dong, Han Tian-Cheng, Lu Xiao, Hou Bing, Li Man-Yuan, Yang Gui-Xue, Li Qing-Yuan, Pei Zhi-Hua, Hong Yuan-Yuan, Zhang Ya-Xi, Chen Wei-Zhi, Zheng Hong, He Ji, Dai Ji-Gang
cfDNA methylation, cfDNA mutations, circulating tumor DNA, lung cancer diagnosis, machine learning, protein cancer biomarkers, pulmonary nodules