结肠癌 RNA 加工基因的表征用于预测临床结果。
Characterization of RNA Processing Genes in Colon Cancer for Predicting Clinical Outcomes.
发表日期:2024
作者:
Jianwen Hu, Yingze Ning, Yongchen Ma, Lie Sun, Guowei Chen
来源:
GENES & DEVELOPMENT
摘要:
结肠癌与多个水平的分子异质性相关。 RNA 加工将初级转录 RNA 转化为成熟 RNA,从而驱动肿瘤发生及其维持。结肠癌中RNA加工基因的特征亟待阐明。在本研究中,我们从癌症基因组图谱(TCGA)和基因表达综合(GEO)数据库中获取了1033个相关样本,以探讨结肠癌中RNA加工表型的异质性癌症。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出具有特定临床结果和生物学特征的 4 个亚型。接下来,我们采用最小绝对收缩和选择算子(LASSO)以及带有惩罚的Cox回归模型来表征RNA加工相关的预后特征。基于FXR1、MFAP1、RBM17等10个基因的RNA加工相关的预后风险模型最终鉴定出SAGE1、SNRPA1、SRRM4、ADAD1、DDX52、ERI1和EXOSC7。通过将此特征与其余临床变量(包括 TNM、年龄、性别和分期)相结合,构建了复合预后列线图。还通过生物信息学方法分析了遗传变异、通路激活和具有风险特征的免疫异质性。结果表明,与低风险组相比,高风险亚组与较高的基因组不稳定性、增加的增殖和周期特征、减少的肿瘤杀伤性 CD8 T 细胞和较差的临床预后相关。这种基于 RNA 编辑基因的预后分类器有助于分层根据 TNM 和临床结果、遗传变异、通路激活和免疫异质性,将结肠癌分为特定亚组。它可用于与当前精准医学标准相当的诊断、分类和靶向治疗策略。它为阐明 RNA 编辑基因的作用及其作为预后标志物在结肠癌中的临床意义提供了基本原理。© The Author(s) 2024。
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.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.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.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.© The Author(s) 2024.