Song Li, Wang Shouguo, Li Qiankun, Lu Yao, Yang Rungong, Feng Xianqi
Academy of Advanced Interdisciplinary Studies, Qilu University of Technology, (Shandong Academy of Sciences), Jinan, Shandong 250353, China.
Department of Tissue Repair and Regeneration, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.
J Oncol. 2023 Mar 8;2023:9931419. doi: 10.1155/2023/9931419. eCollection 2023.
5-methylcytosine (m5C) is a major site of RNA methylation modification, and its abnormal modification is associated with the development of gastric cancer (GC). This study aimed to explore the value of m5C-related genes on the prognosis of GC patients through bioinformatics.
First, m5C-related genes were obtained by nonnegative matrix factorization (NMF) analysis and differentially expressed analysis. The m5C-related model was established and validated in distinct datasets. Moreover, a differential analysis of risk scores according to clinical characteristics was performed. The enrichment analysis was carried out to elucidate the underlying molecular mechanisms. Furthermore, we calculated the differences in immunotherapy and chemotherapy sensitivity between the high- and low-risk groups. Finally, we validated the expression levels of identified model genes by quantitative real-time polymerase chain reaction (qRT-PCR).
A total of five m5C-related subtypes of GC patients in the TCGA database were identified. The m5C-related model was constructed based on APOD, ASCL2, MFAP2, and CREB3L3. Functional enrichment revealed that the m5C-related model might involve in the cell cycle and cell adhesion. Moreover, the high-risk group had a higher abundance of stromal and immune cells in malignant tumor tissues and a lower tumor purity than the low-risk group. The patients in the high-risk group were more sensitive to chemotherapy and had better sensitivity to CTLA4 inhibitors. Furthermore, qRT-PCR results from our specimens verified an over-expression of ASCL2, CREB3L3, and MFAP2 in the cancer cells compared with the normal cells.
A total of five GC subtypes were identified, and a risk model was constructed based on m5C modification.
5-甲基胞嘧啶（m5C）是RNA甲基化修饰的主要位点，其异常修饰与胃癌（GC）的发生发展相关。本研究旨在通过生物信息学方法探讨m5C相关基因对GC患者预后的价值。
首先，通过非负矩阵分解（NMF）分析和差异表达分析获得m5C相关基因。在不同数据集中建立并验证m5C相关模型。此外，根据临床特征对风险评分进行差异分析。进行富集分析以阐明潜在的分子机制。此外，我们计算了高风险组和低风险组在免疫治疗和化疗敏感性方面的差异。最后，我们通过定量实时聚合酶链反应（qRT-PCR）验证了所鉴定模型基因的表达水平。
在TCGA数据库中总共鉴定出五种GC患者的m5C相关亚型。基于载脂蛋白D（APOD）、无翅型MMTV整合位点家族成员2（ASCL2）、微丝相关蛋白2（MFAP2）和环磷腺苷效应元件结合蛋白3样蛋白3（CREB3L3）构建了m5C相关模型。功能富集分析表明，m5C相关模型可能参与细胞周期和细胞黏附。此外，高风险组恶性肿瘤组织中的基质细胞和免疫细胞丰度高于低风险组，肿瘤纯度低于低风险组。高风险组患者对化疗更敏感，对细胞毒性T淋巴细胞相关抗原4（CTLA4）抑制剂的敏感性更好。此外，我们标本的qRT-PCR结果证实，与正常细胞相比，癌细胞中ASCL2、CREB3L3和MFAP2的表达上调。
共鉴定出五种GC亚型，并基于m5C修饰构建了风险模型。
