Zhang Chi, Xia Jiangnan, Zhang Simiao, Li Jing, Zhou Tian, Hu Kaiwen
Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, P.R. China.
School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.
Oncol Lett. 2023 Mar 10;25(4):169. doi: 10.3892/ol.2023.13755. eCollection 2023 Apr.
N7-Methylguanosine (m7G) modification is important in post-transcriptional regulation. dysregulation of m7G RNA modification has been reported to be markedly associated with cancer. However, its importance in bladder urothelial carcinoma (BLCA) remains poorly characterized. The present study systematically analyzed mRNA gene expression data and clinical information from The Cancer Genome Atlas and further constructed robust risk signatures for the four regulators of m7G RNA modification (nudix hydrolase 11, gem nuclear organelle-associated protein 5, eukaryotic translation initiation factor 3 subunit D and cytoplasmic FMR1 interacting protein 1). The differential expression and cell function of m7G-related genes in bladder cancer cells were verified by reverse transcription-quantitative PCR, Cell Counting Kit-8 and colony formation assays. The four-gene-based model could accurately predict the prognosis of BLCA. Nomogram-based clinical decisions had a higher net benefit compared with that of individual predictors. Through immune infiltration analysis, it was found that immune cell infiltration affected the prognosis of patients with BLCA. Finally, the present study identified potential therapeutics that differ between high and low-risk groups based on four genes. In summary, the current findings revealed an essential role for m7G RNA modification regulators in BLCA, and developed risk signatures as promising prognostic markers in patients with BLCA.
N7-甲基鸟苷(m7G)修饰在转录后调控中至关重要。据报道,m7G RNA修饰失调与癌症显著相关。然而,其在膀胱尿路上皮癌(BLCA)中的重要性仍未得到充分表征。本研究系统分析了来自癌症基因组图谱的mRNA基因表达数据和临床信息,并进一步构建了m7G RNA修饰的四个调节因子(Nudix水解酶11、宝石核细胞器相关蛋白5、真核翻译起始因子3亚基D和细胞质FMR1相互作用蛋白1)的稳健风险特征。通过逆转录定量PCR、细胞计数试剂盒-8和集落形成试验验证了膀胱癌细胞中m7G相关基因的差异表达和细胞功能。基于四个基因的模型可以准确预测BLCA的预后。与个体预测指标相比,基于列线图的临床决策具有更高的净效益。通过免疫浸润分析发现,免疫细胞浸润影响BLCA患者的预后。最后,本研究确定了基于四个基因的高风险组和低风险组之间潜在的治疗方法。总之,目前的研究结果揭示了m7G RNA修饰调节因子在BLCA中的重要作用,并开发了风险特征作为BLCA患者有前景的预后标志物。