Cai Ling, Wu Fangjiang, Zhou Qinbo, Gao Ying, Yao Bo, DeBerardinis Ralph J, Acquaah-Mensah George K, Aidinis Vassilis, Beane Jennifer E, Biswal Shyam, Chen Ting, Concepcion-Crisol Carla P, Grüner Barbara M, Jia Deshui, Jones Robert A, Kurie Jonathan M, Lee Min Gyu, Lindahl Per, Lissanu Yonathan, Lorz Corina, MacPherson David, Martinelli Rosanna, Mazur Pawel K, Mazzilli Sarah A, Mii Shinji, Moll Herwig P, Moorehead Roger A, Morrisey Edward E, Ng Sheng Rong, Oser Matthew G, Pandiri Arun R, Powell Charles A, Ramadori Giorgio, Santos Mirentxu, Snyder Eric L, Sotillo Rocio, Su Kang-Yi, Taki Tetsuro, Taparra Kekoa, Tran Phuoc T, Xia Yifeng, van Veen J Edward, Winslow Monte M, Xiao Guanghua, Rudin Charles M, Oliver Trudy G, Xie Yang, Minna John D
Quantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, Texas.
Children's Research Institute, UT Southwestern Medical Center, Dallas, Texas.
Cancer Res. 2025 May 15;85(10):1769-1783. doi: 10.1158/0008-5472.CAN-24-1607.
Lung cancer, the leading cause of cancer mortality, exhibits diverse histologic subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. In this study, we established the Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMM), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors produced a robust and comprehensive database, enhancing the fidelity of the genetic landscape it depicts. The LCAMGDB aligned 859 tumors from GEMMs with human lung cancer mutations, enabling comparative analysis and revealing a pressing need to broaden the diversity of genetic aberrations modeled in the GEMMs. To accompany this resource, a web application was developed that offers researchers intuitive tools for in-depth gene expression analysis. With standardized reprocessing of gene expression data, the LCAMGDB serves as a powerful platform for cross-study comparison and lays the groundwork for future research, aiming to bridge the gap between mouse models and human lung cancer for improved translational relevance. Significance: The Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB) provides a comprehensive and accessible resource for the research community to investigate lung cancer biology in mouse models.
肺癌是癌症死亡的主要原因,具有多种组织学亚型和基因复杂性。已经开发了许多临床前小鼠模型来研究肺癌,但这些模型的数据分散、孤立,难以集中进行比较。在本研究中,我们建立了肺癌原位模型基因表达数据库(LCAMGDB),这是一个广泛的数据库,包含来自77个转录组数据集的1354个样本,其中包括来自基因工程小鼠模型(GEMM)的974个样本、致癌物诱导模型的368个样本和自发模型的12个样本。通过精心整理以及与数据提供者的合作,生成了一个强大而全面的数据库,提高了其所描绘的基因图谱的保真度。LCAMGDB将来自GEMM的859个肿瘤与人类肺癌突变进行比对,能够进行比较分析,并揭示了迫切需要扩大GEMM中所模拟的基因畸变的多样性。为配合这一资源,开发了一个网络应用程序,为研究人员提供直观的工具以进行深入的基因表达分析。通过对基因表达数据进行标准化的重新处理,LCAMGDB成为了跨研究比较的强大平台,并为未来的研究奠定了基础,旨在弥合小鼠模型与人类肺癌之间的差距,以提高转化相关性。意义:肺癌原位模型基因表达数据库(LCAMGDB)为研究界在小鼠模型中研究肺癌生物学提供了一个全面且易于获取的资源。