肺腺癌演化的癌变时间估算：解读肿瘤进化的时间轴
Cancerous time estimation for interpreting the evolution of lung adenocarcinoma
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影响因子:7.7
分区:生物学2区 / 数学与计算生物学1区 生化研究方法2区
发表日期:2024 Sep 23
作者:
Yourui Han, Bolin Chen, Jun Bian, Ruiming Kang, Xuequn Shang
DOI:
10.1093/bib/bbae520
摘要
肺腺癌的进化伴随着大量基因突变和功能障碍，导致其表型状态和进化方向极为复杂。为理解肺腺癌的演化历程，已有多种方法旨在揭示其分子发病机制和功能演变过程。然而，这些方法多受限于缺乏癌变的时间信息以及肿瘤异质性带来的挑战。本研究提出一种患者类潜在景观方法，用以估算在演化过程中不同表型状态出现的癌变时间。随后，基于癌变时间和突变，识别出39条不同的肿瘤发生路径，反映肺腺癌的分子发病机制。通过合并这些路径，获得三种共通的肿瘤演化图谱，描绘了肺腺癌的演化模式。将患者根据癌变时间均匀划分为早期、中期和晚期三个演化阶段，建立了肺腺癌的功能演化网络。通过通路富集分析，从网络中识别出六个关键的功能演化过程，为理解肺腺癌的发展提供重要的科学依据。
Abstract
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.