Department of Endocrinology, Shenzhen Longhua District Central Hospital, Shenzhen 518110, Guangdong, China.
Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, Hunan, China.
Medicine (Baltimore). 2024 Jun 21;103(25):e38623. doi: 10.1097/MD.0000000000038623.
The incidence of papillary thyroid carcinoma (PTC) has increased significantly in recent years, and for patients with metastatic and recurrent PTC, the options for treatment currently available are insufficient. To date, the exact molecular mechanism underlying PTC is still not fully understood. 5-Methylcytosine (m5C) RNA methylation is associated with the prognosis of a variety of tumors. However, the molecular mechanisms and biomarkers associated with m5C in the diagnosis, treatment, and prognosis of this disease have not been fully elucidated. Ten m5C regulators with significantly different expression levels were included in this study. Immune infiltration analysis revealed significant negative correlations between most of these regulators and regulatory T cells. TRDMT1, NSUN5, and NSUN6 had high weights and strong correlations in the protein-protein interaction network. Using gene ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis, 1489 differentially expressed genes were screened from The Cancer Genome Atlas messenger RNA matrix, indicating that these differentially expressed genes were significantly enriched in various pathways and functions related to cancers. Four m5C regulators, NSUN2, NSUN4, NSUN6, and DNMT3B, were screened as prognostic markers by least absolute shrinkage and selection operator regression analysis, and NSUN2 and NSUN6 were identified as risk factors for poor prognosis. We found that the prognostic prediction model constructed using the m5C regulators NSUN2, NSUN4, NSUN6, and DNMT3B showed good prognostic prediction ability and diagnostic ability. This model was applied to predict the survival probability of patients with PTC, the prediction ability of 5-year survival was the best. The multi-factor prognostic prediction model combined with the tumor node metastasis stage and risk score grouping showed better prognostic predictive power.
甲状腺乳头状癌（PTC）的发病率近年来显著增加，对于转移性和复发性 PTC 患者，目前可用的治疗选择不足。迄今为止，PTC 的确切分子机制仍不完全清楚。5-甲基胞嘧啶（m5C）RNA 甲基化与多种肿瘤的预后相关。然而，m5C 在该疾病的诊断、治疗和预后中的分子机制和生物标志物尚未完全阐明。本研究纳入了 10 个表达水平差异显著的 m5C 调节剂。免疫浸润分析显示，这些调节剂中的大多数与调节性 T 细胞之间存在显著的负相关。TRDMT1、NSUN5 和 NSUN6 在蛋白质-蛋白质相互作用网络中具有较高的权重和较强的相关性。使用基因本体、京都基因与基因组百科全书和基因集富集分析，从癌症基因组图谱信使 RNA 矩阵中筛选出 1489 个差异表达基因，表明这些差异表达基因在与癌症相关的各种途径和功能中显著富集。最小绝对收缩和选择算子回归分析筛选出 4 个 m5C 调节剂，包括 NSUN2、NSUN4、NSUN6 和 DNMT3B，作为预后标志物，NSUN2 和 NSUN6 被鉴定为预后不良的危险因素。我们发现，使用 m5C 调节剂 NSUN2、NSUN4、NSUN6 和 DNMT3B 构建的预后预测模型具有良好的预后预测能力和诊断能力。该模型应用于预测 PTC 患者的生存概率，5 年生存率的预测能力最佳。结合肿瘤淋巴结转移分期和风险评分分组的多因素预后预测模型显示出更好的预后预测能力。
