Huang Zhidong, Pan Junfan, Wang Helin, Du Xianqiang, Xu Yusheng, Wang Zhitang, Chen Debo
Quanzhou First Hospital of Fujian Medical University, Quanzhou, China.
Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Front Cell Dev Biol. 2021 Apr 13;9:657547. doi: 10.3389/fcell.2021.657547. eCollection 2021.
The m5C RNA methylation regulators are closely related to tumor proliferation, occurrence, and metastasis. This study aimed to investigate the gene expression, clinicopathological characteristics, and prognostic value of m5C regulators in triple-negative breast cancer (TNBC) and their correlation with the tumor immune microenvironment (TIM).
The TNBC data, Luminal BC data and HER2 positive BC data set were obtained from The Cancer Genome Atlas and Gene Expression Omnibus, and 11 m5C RNA methylation regulators were analyzed. Univariate Cox regression and the least absolute shrinkage and selection operator regression models were used to develop a prognostic risk signature. The UALCAN and cBioportal databases were used to analyze the gene characteristics and gene alteration frequency of prognosis-related m5C RNA methylation regulators. Gene set enrichment analysis was used to analyze cellular pathways enriched by prognostic factors. The Tumor Immune Single Cell Hub (TISCH) and Timer online databases were used to explore the relationship between prognosis-related genes and the TIM.
Most of the 11 m5C RNA methylation regulators were differentially expressed in TNBC and normal samples. The prognostic risk signature showed good reliability and an independent prognostic value. Prognosis-related gene mutations were mainly amplified. Concurrently, the NOP2/Sun domain family member 2 () upregulation was closely related to spliceosome, RNA degradation, cell cycle signaling pathways, and RNA polymerase. Meanwhile, downregulation was related to extracellular matrix receptor interaction, metabolism, and cell adhesion. Analysis of the TISCH and Timer databases showed that prognosis-related genes affected the TIM, and the subtypes of immune-infiltrating cells differed between and .
Regulatory factors of m5C RNA methylation can predict the clinical prognostic risk of TNBC patients and affect tumor development and the TIM. Thus, they have the potential to be a novel prognostic marker of TNBC, providing clues for understanding the RNA epigenetic modification of TNBC.
m5C RNA甲基化调节因子与肿瘤增殖、发生和转移密切相关。本研究旨在探讨m5C调节因子在三阴性乳腺癌（TNBC）中的基因表达、临床病理特征和预后价值，以及它们与肿瘤免疫微环境（TIM）的相关性。
从癌症基因组图谱和基因表达综合数据库中获取TNBC数据集、Luminal型乳腺癌数据集和HER2阳性乳腺癌数据集，并分析11个m5C RNA甲基化调节因子。采用单因素Cox回归和最小绝对收缩和选择算子回归模型建立预后风险特征。利用UALCAN和cBioportal数据库分析预后相关m5C RNA甲基化调节因子的基因特征和基因改变频率。基因集富集分析用于分析预后因素富集的细胞通路。利用肿瘤免疫单细胞中心（TISCH）和Timer在线数据库探讨预后相关基因与TIM的关系。
11个m5C RNA甲基化调节因子中的大多数在TNBC和正常样本中差异表达。预后风险特征显示出良好的可靠性和独立的预后价值。预后相关基因突变主要为扩增。同时，NOP2/Sun结构域家族成员2（）上调与剪接体、RNA降解、细胞周期信号通路和RNA聚合酶密切相关。同时，下调与细胞外基质受体相互作用、代谢和细胞黏附有关。TISCH和Timer数据库分析表明，预后相关基因影响TIM，免疫浸润细胞亚型在和之间存在差异。
m5C RNA甲基化的调节因子可以预测TNBC患者的临床预后风险，并影响肿瘤发展和TIM。因此，它们有可能成为TNBC的新型预后标志物，为理解TNBC的RNA表观遗传修饰提供线索。
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