Cheng Xu, Yi Xuanzi
Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
Department of General Practice, The Third-Xiangya Hospital, Central South University, Changsha, China.
Front Genet. 2023 Jan 18;13:1065424. doi: 10.3389/fgene.2022.1065424. eCollection 2022.
RNA modifications are important in the study of epigenetic regulatory mechanisms in immune responses and tumorigenesis. When RNA writers are mutated or disrupted in expression, the genes associated with the pathways they modify are also disrupted and can activate or repress related pathways, affecting tumorigenesis and progression. However, the potential role of RNA writers in prostate cancer is unclear. Based on data from three datasets, we describe 26 RNA writers that mediate gene expression and genetic mutation in prostate cancer and assess their expression patterns in 948 prostate cancer samples. Using principal component analysis algorithms, the RM Score was developed to quantify the RNA modification patterns of specific tumors. Two different categories were determined by unsupervised clustering methods, and survival analysis showed significant differences in OS prognosis between these two categories. Differentially expressed genes between the different categories were detected and the RNA writers-mediated scoring model RM_Score were constructed based on this. Also, the RM_Score was analyzed in relation to clinical characteristics, immune infiltration level, drug response, and efficacy of chemotherapy and immunotherapy. Those results confirm that multilayer alterations in epitope-modified RNA writers are associated with patient prognosis and with immune cell infiltration characteristics. Finally, we examined differentially expressed mRNA, lncRNA and miRNA between high and low RM_Score groups, based on which a ceRNA regulatory network was constructed. This work is a comprehensive analysis of modified writers in prostate cancer and identified them to have a role in chemotherapy and immunotherapy.
RNA修饰在免疫反应和肿瘤发生的表观遗传调控机制研究中具有重要意义。当RNA书写器发生突变或表达受到干扰时，与它们所修饰的通路相关的基因也会受到干扰，进而可能激活或抑制相关通路，影响肿瘤的发生和进展。然而，RNA书写器在前列腺癌中的潜在作用尚不清楚。基于三个数据集的数据，我们描述了26种在前列腺癌中介导基因表达和基因突变的RNA书写器，并评估了它们在948例前列腺癌样本中的表达模式。使用主成分分析算法，开发了RM评分来量化特定肿瘤的RNA修饰模式。通过无监督聚类方法确定了两个不同的类别，生存分析显示这两个类别在总生存期预后方面存在显著差异。检测了不同类别之间的差异表达基因，并据此构建了RNA书写器介导的评分模型RM_Score。此外，还分析了RM_Score与临床特征、免疫浸润水平、药物反应以及化疗和免疫治疗疗效的关系。这些结果证实，表位修饰的RNA书写器的多层改变与患者预后以及免疫细胞浸润特征相关。最后，我们检测了高RM_Score组和低RM_Score组之间差异表达的mRNA、lncRNA和miRNA，并据此构建了ceRNA调控网络。这项工作是对前列腺癌中修饰书写器的全面分析，并确定它们在化疗和免疫治疗中发挥作用。
