Journal Article

Integrated multiomics signatures to optimize the accurate diagnosis of lung cancer

Guo, Liuning, Sun, Xiwen, Yang, Minglei, Chen, Tao, She, Yunlang, Song, Yongxiang, Zhao, Mengmeng, Zhao, Guofang, Deng, Jiajun, Hu, Xinlei, Yu, Bentong, Ma, Minjie, He, Bingxi, Wang, Tingting, Xie, Dan, Qu, Wendong, Zhao, Deping, He, Yiming, Yan, Ziyue, Chen, Chang, Liu, Lunxu, Zhong, Yifan, Wang, Yang, Xue, Gang, Li, Shenghui, Zhang, Jun

2025

Overview

Diagnosing lung cancer from indeterminate pulmonary nodules (IPLs) remains challenging. In this multi-institutional study involving 2032 participants with IPLs, we integrate the clinical, radiomic with circulating cell-free DNA fragmentomic features in 5-methylcytosine (5mC)-enriched regions to establish a multiomics model (clinic-RadmC) for predicting the malignancy risk of IPLs. The clinic-RadmC yields an area-under-the-curve (AUC) of 0.923 on the external test set, outperforming the single-omics models, and models that only combine clinical features with radiomic, or fragmentomic features in 5mC-enriched regions ( p  < 0.050 for all). The superiority of the clinic-RadmC maintains well even after adjusting for clinic-radiological variables. Furthermore, the clinic-RadmC-guided strategy could reduce the unnecessary invasive procedures for benign IPLs by 10.9% ~ 35%, and avoid the delayed treatment for lung cancer by 3.1% ~ 38.8%. In summary, our study indicates that the clinic-RadmC provides a more effective and noninvasive tool for optimizing lung cancer diagnoses, thus facilitating the precision interventions. Diagnosis of lung cancer from indeterminate pulmonary nodules remains challenging. Here, the authors develop a multi-omics signature to identify oncogenic nodules, and prevent unnecessary procedures.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 49/22 / 49/23 / 5-Methylcytosine - metabolism / 631/67/1612 / 631/67/2322 / 692/53/2421 / Aged / Biological analysis / Biomarkers, Tumor - genetics / Cell-Free Nucleic Acids - genetics / Diagnosis / DNA Methylation / Female / Genomics - methods / Humanities and Social Sciences / Humans / Lung cancer / Lung Neoplasms - diagnosis / Lung Neoplasms - genetics / Lung nodules / Male / Malignancy / Middle Aged / multidisciplinary / Multiomics / Nodules / Optimization / Radiomics / Science / Science (multidisciplinary)