Chen Mei, Nie Zhenyu, Gao Yuanhui, Cao Hui, Zheng Linlin, Guo Na, Peng Yanling, Zhang Shufang
Central Laboratory, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, China.
Front Pharmacol. 2022 Sep 6;13:900006. doi: 10.3389/fphar.2022.900006. eCollection 2022.
RNA methylation modification plays an important role in immune regulation. m7G RNA methylation is an emerging research hotspot in the RNA methylation field. However, its role in the tumor immune microenvironment of kidney renal clear cell carcinoma (KIRC) is still unclear. We analyzed the expression profiles of 29 m7G regulators in KIRC, integrated multiple datasets to identify a novel m7G regulator-mediated molecular subtype, and developed the m7G score. We evaluated the immune tumor microenvironments in m7G clusters and analyzed the correlation of the m7G score with immune cells and drug sensitivity. We tested the predictive power of the m7G score for prognosis of patients with KIRC and verified the predictive accuracy of the m7G score by using the GSE40912 and E-MTAB-1980 datasets. The genes used to develop the m7G score were verified by qRT-PCR. Finally, we experimentally analyzed the effects of WDR4 knockdown on KIRC proliferation, migration, invasion, and drug sensitivity. We identified three m7G clusters. The expression of m7G regulators was higher in cluster C than in other clusters. m7G cluster C was related to immune activation, low tumor purity, good prognosis, and low m7G score. Cluster B was related to drug metabolism, high tumor purity, poor survival, and high m7G score. Cluster A was related to purine metabolism. The m7G score can well-predict the prognosis of patients with KIRC, and its prediction accuracy based on the m7G score nomogram was very high. Patients with high m7G scores were more sensitive to rapamycin, gefitinib, sunitinib, and vinblastine than other patients. Knocking down WDR4 can inhibit the proliferation, migration, and invasion of 786-0 and Caki-1 cells and increase sensitivity to sorafenib and sunitinib. We proposed a novel molecular subtype related to m7G modification and revealed the immune cell infiltration characteristics of different subtypes. The developed m7G score can well-predict the prognosis of patients with KIRC, and our research provides a basis for personalized treatment of patients with KIRC.
RNA甲基化修饰在免疫调节中发挥着重要作用。m7G RNA甲基化是RNA甲基化领域一个新兴的研究热点。然而，其在肾透明细胞癌（KIRC）肿瘤免疫微环境中的作用仍不清楚。我们分析了KIRC中29种m7G调节因子的表达谱，整合多个数据集以鉴定一种新型的m7G调节因子介导的分子亚型，并开发了m7G评分。我们评估了m7G簇中的免疫肿瘤微环境，并分析了m7G评分与免疫细胞和药物敏感性的相关性。我们测试了m7G评分对KIRC患者预后的预测能力，并通过使用GSE40912和E-MTAB-1980数据集验证了m7G评分的预测准确性。通过qRT-PCR验证了用于开发m7G评分的基因。最后，我们通过实验分析了WDR4敲低对KIRC增殖、迁移、侵袭和药物敏感性的影响。我们鉴定出三个m7G簇。m7G调节因子在C簇中的表达高于其他簇。m7G C簇与免疫激活、低肿瘤纯度、良好预后和低m7G评分相关。B簇与药物代谢、高肿瘤纯度、较差生存和高m7G评分相关。A簇与嘌呤代谢相关。m7G评分能够很好地预测KIRC患者的预后，基于m7G评分列线图的预测准确性非常高。m7G评分高的患者比其他患者对雷帕霉素、吉非替尼、舒尼替尼和长春碱更敏感。敲低WDR4可抑制786-0和Caki-1细胞的增殖、迁移和侵袭，并增加对索拉非尼和舒尼替尼的敏感性。我们提出了一种与m7G修饰相关的新型分子亚型，并揭示了不同亚型的免疫细胞浸润特征。开发的m7G评分能够很好地预测KIRC患者的预后，我们的研究为KIRC患者的个体化治疗提供了依据。
