肺腺癌的进化伴随着大量的基因突变和功能障碍，使其表型状态和进化方向高度复杂。为了解释肺腺癌的进化，已经开发了多种方法来阐明分子发病机制和功能进化过程。然而，这些方法大多数都受到癌症时间信息的缺乏以及异质特征的挑战的限制。为了解决这些问题，本研究提出了一种患者准电位景观方法来估计进化过程中表型状态出现的癌变时间。随后，根据癌变时间和突变情况，共鉴定出39条不同的致癌路径，反映了肺腺癌进化过程的分子发病机制。为了解释肺腺癌的进化模式，通过合并癌基因路径，获得了三种癌基因图作为共同的进化模式。此外，根据癌变时间将患者均匀地重新划分为早期、中期和晚期进化阶段，并建立了可行的框架来构建肺腺癌的功能进化网络。基于通路富集分析，从功能进化网络中总共识别出了六个重要的功能进化过程，这在理解肺腺癌的发展中发挥着关键作用。©作者2024。由牛津大学出版社出版。

The evolution of lung adenocarcinoma is accompanied by a multitude of gene mutations and dysfunctions, rendering its phenotypic state and evolutionary direction highly complex. To interpret the evolution of lung adenocarcinoma, various methods have been developed to elucidate the molecular pathogenesis and functional evolution processes. However, most of these methods are constrained by the absence of cancerous temporal information, and the challenges of heterogeneous characteristics. To handle these problems, in this study, a patient quasi-potential landscape method was proposed to estimate the cancerous time of phenotypic states' emergence during the evolutionary process. Subsequently, a total of 39 different oncogenetic paths were identified based on cancerous time and mutations, reflecting the molecular pathogenesis of the evolutionary process of lung adenocarcinoma. To interpret the evolution patterns of lung adenocarcinoma, three oncogenetic graphs were obtained as the common evolutionary patterns by merging the oncogenetic paths. Moreover, patients were evenly re-divided into early, middle, and late evolutionary stages according to cancerous time, and a feasible framework was developed to construct the functional evolution network of lung adenocarcinoma. A total of six significant functional evolution processes were identified from the functional evolution network based on the pathway enrichment analysis, which plays critical roles in understanding the development of lung adenocarcinoma.© The Author(s) 2024. Published by Oxford University Press.