Li Kai, Wang Weixing
Department of Gastrointestinal Surgery Ⅱ, Renmin Hospital of Wuhan University, Wuhan, China.
Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
Front Genet. 2022 Oct 14;13:981392. doi: 10.3389/fgene.2022.981392. eCollection 2022.
N7-methylguanosine (m7G) is an emerging research hotspot in the field of RNA methylation, and its role in tumor regulation is becoming increasingly recognized. However, its role in colorectal cancer (CRC) remains unclear. Hence, our study explored the role of m7G in CRC. The mRNA expression data and the corresponding clinical information of the patients with CRC were obtained from The Cancer Genome Atlas (TCGA). A m7G-related gene pair signature was established using the Cox and LASSO regression analyses. A series of analyses based on the signature included analysis of prognosis, correlation analysis, immune-related analysis, and estimation of tumor mutational burden (TMB), microsatellite instability (MSI), and response to immunotherapy. A nomogram prediction model was then constructed. In total, 2156 m7G-related gene pairs were screened based on 152 m7G-related genes. Then, a prognostic signature of seven gene pairs was constructed, and the patients were stratified into high- or low-risk groups. Better overall survival (OS), left-sided tumor, early stage, immune activity, and low proportion of MSI-low and MSI-high were all associated with a low risk score. High-risk patients had a higher TMB, and patients with a high TMB had a poor OS. Furthermore, the risk score was linked to immune checkpoint expression (including PD-L1), the tumor immune dysfunction and exclusion (TIDE) score, and chemotherapy sensitivity. We also created an accurate nomogram to increase the clinical applicability of the risk score. We identified an m7G pair-based prognostic signature associated with prognosis, immune landscape, immunotherapy, and chemotherapy in CRC. These findings could help us to better understand the role of m7G in CRC, as well as pave the path for novel methods to assess prognosis and design more effective individualized therapeutic strategies.
N7-甲基鸟苷（m7G）是RNA甲基化领域一个新兴的研究热点，其在肿瘤调控中的作用日益受到认可。然而，其在结直肠癌（CRC）中的作用仍不清楚。因此，我们的研究探讨了m7G在CRC中的作用。从癌症基因组图谱（TCGA）获取了CRC患者的mRNA表达数据及相应临床信息。使用Cox和LASSO回归分析建立了一个与m7G相关的基因对特征。基于该特征进行的一系列分析包括预后分析、相关性分析、免疫相关分析以及肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）和免疫治疗反应的评估。然后构建了一个列线图预测模型。基于152个与m7G相关的基因，共筛选出2156个与m7G相关的基因对。随后构建了一个由七个基因对组成的预后特征，并将患者分为高风险或低风险组。更好的总生存期（OS）、左侧肿瘤、早期阶段、免疫活性以及低比例的微卫星低度不稳定（MSI-low）和微卫星高度不稳定（MSI-high）均与低风险评分相关。高风险患者的TMB较高，而TMB高的患者OS较差。此外，风险评分与免疫检查点表达（包括程序性死亡受体配体1（PD-L1））、肿瘤免疫功能障碍和排除（TIDE）评分以及化疗敏感性相关。我们还创建了一个准确的列线图以提高风险评分的临床适用性。我们鉴定出了一个基于m7G对的预后特征，其与CRC的预后、免疫格局、免疫治疗和化疗相关。这些发现有助于我们更好地理解m7G在CRC中的作用，也为评估预后的新方法以及设计更有效的个体化治疗策略铺平了道路。
