Li Jianrong, Li Chu, Li Xiaolian, Chen Yuling, Li Zhangfu, Lin Yuntao, Jing Huan, Wang Yufan, Yang Hongyu
School of Stomatology, Zunyi Medical University, Zunyi, Guizhou 563000, China.
Department of Oral and Maxillofacial Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, China.
J Cancer. 2024 Sep 30;15(18):6022-6037. doi: 10.7150/jca.98350. eCollection 2024.
N7-methylguanosine (m7G) methyltransferases and microRNAs (miRNAs) are closely associated with tumor progression. However, the role of m7G methyltransferase-related miRNAs as prognostic markers in oral squamous cell carcinoma (OSCC) has not been studied. This study aimed to explore the m7G methyltransferase-related miRNAs in OSCC, establish a prognostic model based on m7G methyltransferase-related miRNAs, investigate their correlation with immune cell infiltration, and assess their potential prognostic value. Transcriptional and clinical data of patients with OSCC were obtained from The Cancer Genome Atlas (TCGA) database. TargetScan and miRWalk were used to predict m7G methyltransferase-related miRNAs. Subsequently, differentially expressed m7G methyltransferase-related miRNAs in TCGA-OSCC were selected. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to build an m7G methyltransferase-related miRNA risk prognostic model for TCGA-OSCC. Patients were stratified into high- and low-risk groups. The predictive and diagnostic accuracies of the risk prognostic model were further validated using Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curve analysis, independent prognosis analysis, and nomogram plots. Finally, quantitative real-time polymerase chain reaction (qPCR) was used to validate the expression levels of m7G methyltransferase-related miRNAs in postoperative cancer and adjacent normal tissues from 60 patients with OSCC. Through Cox and LASSO regression analysis, six candidate miRNAs (hsa-miR-338-3p, hsa-miR-1251-3p, hsa-miR-3129-5p, hsa-miR-4633-3p, hsa-miR-216a-3p, and hsa-miR-6503-3p) most relevant to the prognosis of patients with OSCC were identified to construct an m7G methyltransferase-related miRNA risk prognostic model. In this model, the overall survival (OS) of the high-risk group was significantly shorter than that of the low-risk group (P < 0.001). The model effectively predicted prognosis and served as an independent prognostic indicator for patients with OSCC. Compared with the low-risk group, the high-risk group exhibited a significantly increased capacity for immune cell infiltration (P < 0.05), while the activation and initiation abilities of immune cells were decreased. Finally, six m7G methyltransferase-related miRNAs were validated in OSCC tissue samples. The risk prognostic model based on six m7G methyltransferase-related miRNAs can predict the OS rate of patients with OSCC and has the potential to guide individualized treatment. This prognostic model is closely associated with immune cell infiltration in patients with OSCC.
N7-甲基鸟苷（m7G）甲基转移酶与微小RNA（miRNA）与肿瘤进展密切相关。然而，m7G甲基转移酶相关miRNA作为口腔鳞状细胞癌（OSCC）预后标志物的作用尚未得到研究。本研究旨在探索OSCC中m7G甲基转移酶相关miRNA，建立基于m7G甲基转移酶相关miRNA的预后模型，研究它们与免疫细胞浸润的相关性，并评估其潜在的预后价值。从癌症基因组图谱（TCGA）数据库中获取OSCC患者的转录组和临床数据。使用TargetScan和miRWalk预测m7G甲基转移酶相关miRNA。随后，筛选出TCGA-OSCC中差异表达的m7G甲基转移酶相关miRNA。采用Cox回归和最小绝对收缩与选择算子（LASSO）回归分析构建TCGA-OSCC的m7G甲基转移酶相关miRNA风险预后模型。将患者分为高风险组和低风险组。使用Kaplan-Meier生存分析、受试者工作特征（ROC）曲线分析、独立预后分析和列线图进一步验证风险预后模型的预测和诊断准确性。最后，采用定量实时聚合酶链反应（qPCR）验证60例OSCC患者术后癌组织和癌旁正常组织中m7G甲基转移酶相关miRNA的表达水平。通过Cox和LASSO回归分析，确定了与OSCC患者预后最相关的6个候选miRNA（hsa-miR-338-3p、hsa-miR-1251-3p、hsa-miR-3129-5p、hsa-miR-4633-3p、hsa-miR-216a-3p和hsa-miR-6503-3p），构建了m7G甲基转移酶相关miRNA风险预后模型。在该模型中，高风险组的总生存期（OS）显著短于低风险组（P<0.001）。该模型有效预测了预后，并可作为OSCC患者的独立预后指标。与低风险组相比，高风险组免疫细胞浸润能力显著增强（P<0.05），而免疫细胞的激活和启动能力下降。最后，在OSCC组织样本中验证了6个m7G甲基转移酶相关miRNA。基于6个m7G甲基转移酶相关miRNA的风险预后模型可以预测OSCC患者的OS率，并具有指导个体化治疗的潜力。该预后模型与OSCC患者的免疫细胞浸润密切相关。
