Abstract:
Colorectal cancer (CRC) intricacies, involving dysregulated cellular processes and programmed cell death (PCD), are explored in the context of N6-methyladenosine (m6A) RNA modification. Utilizing the TCGA-COADREAD/CRC cohort, 854 m6A-related PCD genes are identified, forming the basis for a robust 10-gene risk model (CDRS) established through LASSO Cox regression. qPCR experiments using CRC cell lines and fresh tissues was performed for validation. The CDRS served as an independent risk factor for CRC and showed significant associations with clinical features, molecular subtypes, and overall survival in multiple datasets. Moreover, CDRS surpasses other predictors, unveiling distinct genomic profiles, pathway activations, and associations with the tumor microenvironment. Notably, CDRS exhibits predictive potential for drug sensitivity, presenting a novel paradigm for CRC risk stratification and personalized treatment avenues.
摘要:
大肠癌(CRC)的复杂性,涉及失调的细胞过程和程序性细胞死亡(PCD),在N6-甲基腺苷(m6A)RNA修饰的背景下进行了探索。利用TCGA-COADREAD/CRC队列,鉴定了854个m6A相关的PCD基因,形成通过LASSOCox回归建立的稳健10基因风险模型(CDRS)的基础。使用CRC细胞系和新鲜组织进行qPCR实验用于验证。CDRS是CRC的独立危险因素,与临床特征显著相关。分子亚型,和多个数据集中的总体生存率。此外,CDRS超过其他预测因子,揭示独特的基因组图谱,途径激活,以及与肿瘤微环境的关联。值得注意的是,CDRS显示出药物敏感性的预测潜力,提出了一种新的CRC风险分层和个性化治疗途径的范式。