Wang Ziyang, Yuan Xiaoqiu, Sun Kunkun, Wu Fang, Liu Ke, Jin Yiruo, Chervova Olga, Nie Yuntao, Yang Airong, Jin Yichen, Li Jing, Li Yun, Yang Fan, Wang Jun, Beck Stephan, Carbone David, Jiang Guanchao, Chen Kezhong
Department of Thoracic Surgery, Peking University People's Hospital, Beijing, 100044, China.
Thoracic Oncology Institute, Peking University People's Hospital, Beijing, 100044, China.
NPJ Precis Oncol. 2025 Jan 14;9(1):14. doi: 10.1038/s41698-024-00786-5.
Next-generation sequencing (NGS) offers a promising approach for differentiating multiple primary lung cancers (MPLC) from intrapulmonary metastasis (IPM), though panel selection and clonal interpretation remain challenging. Whole-exome sequencing (WES) data from 80 lung cancer samples were utilized to simulate MPLC and IPM, with various sequenced panels constructed through gene subsampling. Two clonal interpretation approaches primarily applied in clinical practice, MoleA (based on shared mutation comparison) and MoleB (based on probability calculation), were subsequently evaluated. ROC analysis highlighted MoleB's superior performance, especially with the NCCNplus panel (AUC = 0.950 ± 0.002) and pancancer MoleA (AUC = 0.792 ± 0.004). In two independent cohorts (WES cohort, N = 42 and non-WES cohort, N = 94), NGS-based methodologies effectively stratified disease-free survival, with NCCNplus MoleB further predicting prognosis. Phylogenetic analysis further revealed evolutionary distinctions between MPLC and IPM, establishing an optimized NGS-based framework for differentiating multiple lung cancers.
下一代测序（NGS）为区分多原发性肺癌（MPLC）和肺内转移（IPM）提供了一种有前景的方法，尽管检测 panel 的选择和克隆解读仍然具有挑战性。利用来自 80 例肺癌样本的全外显子测序（WES）数据来模拟 MPLC 和 IPM，并通过基因二次抽样构建了各种测序 panel。随后评估了两种主要应用于临床实践的克隆解读方法，即 MoleA（基于共享突变比较）和 MoleB（基于概率计算）。ROC 分析突出了 MoleB 的优越性能，特别是对于 NCCNplus panel（AUC = 0.950 ± 0.002）和泛癌 MoleA（AUC = 0.792 ± 0.004）。在两个独立队列（WES 队列，N = 42 和非 WES 队列，N = 94）中，基于 NGS 的方法有效地对无病生存期进行了分层，其中 NCCNplus MoleB 进一步预测了预后。系统发育分析进一步揭示了 MPLC 和 IPM 之间的进化差异，建立了一个优化的基于 NGS 的框架来区分多种肺癌。
