泛癌分析端粒维持机制。
Pan-cancer analysis of telomere maintenance mechanisms.
机构信息
Bioinformatics Group, Institute of Molecular Biology NAS RA, Yerevan, Armenia.
Interdisciplinary Centre for Bioinformatics, University of Leipzig, Leipzig, Germany; Armenian Bioinformatics Institute, Yerevan, Armenia.
出版信息
J Biol Chem. 2024 Jun;300(6):107392. doi: 10.1016/j.jbc.2024.107392. Epub 2024 May 18.
Telomeres, protective caps at chromosome ends, maintain genomic stability and control cell lifespan. Dysregulated telomere maintenance mechanisms (TMMs) are cancer hallmarks, enabling unchecked cell proliferation. We conducted a pan-cancer evaluation of TMM using RNA sequencing data from The Cancer Genome Atlas for 33 different cancer types and analyzed the activities of telomerase-dependent (TEL) and alternative lengthening of telomeres (ALT) TMM pathways in detail. To further characterize the TMM profiles, we categorized the tumors based on their ALT and TEL TMM pathway activities into five major phenotypes: ALT TEL , ALT TEL , ALT TEL , ALT TEL , and ALT TEL . These phenotypes refer to variations in telomere maintenance strategies, shedding light on the heterogeneous nature of telomere regulation in cancer. Moreover, we investigated the clinical implications of TMM phenotypes by examining their associations with clinical characteristics and patient outcomes. Specific TMM profiles were linked to specific survival patterns, emphasizing the potential of TMM profiling as a prognostic indicator and aiding in personalized cancer treatment strategies. Gene ontology analysis of the TMM phenotypes unveiled enriched biological processes associated with cell cycle regulation (both TEL and ALT), DNA replication (TEL), and chromosome dynamics (ALT) showing that telomere maintenance is tightly intertwined with cellular processes governing proliferation and genomic stability. Overall, our study provides an overview of the complexity of transcriptional regulation of telomere maintenance mechanisms in cancer.
端粒是染色体末端的保护帽,可维持基因组稳定性并控制细胞寿命。端粒维持机制(TMMs)失调是癌症的标志,使细胞不受控制地增殖。我们使用来自癌症基因组图谱(TCGA)的 33 种不同癌症类型的 RNA 测序数据对 TMM 进行了泛癌症评估,并详细分析了端粒酶依赖性(TEL)和端粒延长的替代途径(ALT)TMM 途径的活性。为了进一步描述 TMM 谱,我们根据其 ALT 和 TEL TMM 途径活性将肿瘤分为五类主要表型:ALT TEL ,ALT TEL ,ALT TEL ,ALT TEL ,和 ALT TEL 。这些表型指的是端粒维持策略的变化,揭示了癌症中端粒调控的异质性。此外,我们通过检查 TMM 表型与临床特征和患者结局的关联来研究 TMM 表型的临床意义。特定的 TMM 谱与特定的生存模式相关联,强调了 TMM 分析作为预后指标的潜力,并有助于制定个性化的癌症治疗策略。TMM 表型的基因本体分析揭示了与细胞周期调控(TEL 和 ALT)、DNA 复制(TEL)和染色体动力学(ALT)相关的丰富生物学过程,表明端粒维持与控制增殖和基因组稳定性的细胞过程密切相关。总的来说,我们的研究提供了癌症中端粒维持机制转录调控复杂性的概述。