■结肠癌与多个水平的分子异质性有关。RNA加工将初级转录RNA转化为成熟RNA,推动肿瘤发生及其维护。迫切需要阐明结肠癌中RNA加工基因的特征。
■在这项研究中,我们从癌症基因组图谱(TCGA)和基因表达综合(GEO)数据库中获得了1033个相关样本,以探索结肠癌RNA加工表型的异质性.首先,通过对485个RNA加工基因的分析,无监督层次聚类分析检测到4种具有特定临床结果和生物学特征的亚型。接下来,我们采用最小绝对收缩和选择算子(LASSO)以及带惩罚的Cox回归模型来表征RNA加工相关的预后特征.
■最终确定了基于FXR1、MFAP1、RBM17、SAGE1、SNRPA1、SRRM4、ADAD1、DDX52、ERI1和EXOSC7等10个基因的RNA加工相关预后风险模型。通过将该特征与包括TNM在内的其余临床变量相结合,构建了复合预后列线图。年龄,性别,和舞台。遗传变异,通路激活,并通过生物信息学方法分析了具有风险特征的免疫异质性。结果表明,高风险亚组与更高的基因组不稳定性相关,增加的增殖和周期特征,与低危组相比,肿瘤杀伤CD8+T细胞减少,临床预后较差。
■这种基于RNA编辑基因的预后分类器有助于根据TNM和临床结果将结肠癌分为特定的亚组,遗传变异,通路激活,和免疫异质性。它可以用于诊断,分类和有针对性的治疗策略可与当前的精准医学标准相媲美。它为阐明RNA编辑基因的作用及其在结肠癌中作为预后标志物的临床意义提供了理论基础。
UNASSIGNED: Colon cancer is associated with multiple levels of molecular heterogeneity. RNA processing converts primary transcriptional RNA to mature RNA, which drives tumourigenesis and its maintenance. The characterisation of RNA processing genes in colon cancer urgently needs to be elucidated.
UNASSIGNED: In this study, we obtained 1033 relevant samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to explore the heterogeneity of RNA processing phenotypes in colon cancer. Firstly, Unsupervised hierarchical cluster analysis detected 4 subtypes with specific clinical outcomes and biological features via analysis of 485 RNA processing genes. Next, we adopted the least absolute shrinkage and selection operator (LASSO) as well as Cox regression model with penalty to characterise RNA processing-related prognostic features.
UNASSIGNED: An RNA processing-related prognostic risk model based on 10 genes including FXR1, MFAP1, RBM17, SAGE1, SNRPA1, SRRM4, ADAD1, DDX52, ERI1, and EXOSC7 was identified finally. A composite prognostic nomogram was constructed by combining this feature with the remaining clinical variables including TNM, age, sex, and stage. Genetic variation, pathway activation, and immune heterogeneity with risk signatures were also analysed via bioinformatics methods. The outcomes indicated that the high-risk subgroup was associated with higher genomic instability, increased proliferative and cycle characteristics, decreased tumour killer CD8+ T cells and poorer clinical prognosis than the low-risk group.
UNASSIGNED: This prognostic classifier based on RNA-edited genes facilitates stratification of colon cancer into specific subgroups according to TNM and clinical outcomes, genetic variation, pathway activation, and immune heterogeneity. It can be used for diagnosis, classification and targeted treatment strategies comparable to current standards in precision medicine. It provides a rationale for elucidation of the role of RNA editing genes and their clinical significance in colon cancer as prognostic markers.