解释肺腺癌进化的癌症时间估计
Cancerous time estimation for interpreting the evolution of lung adenocarcinoma
影响因子:7.70000
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
摘要
肺腺癌的进化伴随着多种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，已经开发了各种方法来阐明分子发病机理和功能进化过程。但是，这些方法中的大多数受到癌性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，在这项研究中，提出了一种患者准势景观方法，以估计进化过程中表型状态出现的癌症。随后，基于癌变时间和突变，总共鉴定出39种不同的肿瘤途径，这反映了肺腺癌进化过程的分子发病机理。为了解释肺腺癌的进化模式，通过合并致癌路径，获得了三个癌变图作为常见的进化模式。此外，根据癌变时间将患者均匀地重新分布为早期，中期和晚期进化阶段，并开发了可行的框架来构建肺腺癌的功能进化网络。基于途径富集分析，从功能进化网络中确定了总共六个重要的功能进化过程，该过程在理解肺腺癌的发展中起着关键作用。
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.