Zhu Zhenghui, Xie Yuxia, Yin Minhao, Peng Lei, Zhu Hong
Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
J Cancer. 2024 Oct 7;15(18):6086-6102. doi: 10.7150/jca.99173. eCollection 2024.
Colon cancer (CC) is a highly prevalent malignancy worldwide, characterized by elevated mortality rates and poor prognosis. N7-methylguanosine (m7G) methylation is an emerging RNA modification type and involved in the development of many tumors. Despite this, the correlation between m7G-related miRNAs and CC remains to be elucidated. This research aimed to investigate the clinical significance of m7G-related miRNAs in predicting both the prognosis and tumor microenvironment (TME) of CC. We retrieved transcriptome data and associated clinical information from a publicly accessible database. Using univariate Cox and LASSO regression analyses, we established a signature of m7G-related miRNAs. Additionally, we used CIBERSORT and ssGSEA algorithms to explore the association between the prognostic risk score and the TME in CC patients. By considering the risk signature and immune infiltration, we identified differentially expressed genes that contribute to the prognosis of CC. Finally, the expression patterns of prognostic miRNAs were verified using quantitative reverse transcriptase PCR (qRT-PCR) in cell lines. We constructed a prognostic risk signature based on seven m7G-related miRNAs (miR-136-5p, miR-6887-3p, miR-195-5p, miR-149-3p, miR-4433a-5p, miR-31-5p, and miR-129-2-3p). Subsequently, we observed remarkable differences in patient outcomes between the high- and low-risk groups. The area under the curve (AUC) for 1-, 3-, and 5-year survivals in the ROC curve were 0.735, 0.707, and 0.632, respectively. Furthermore, our results showed that the risk score can serve as an independent prognostic biomarker for overall survival prediction. In terms of immune analysis, the results revealed a significant association between the risk signature and immune infiltration, as well as immune checkpoint expression. Finally, our study showed that CCDC160 and RLN3 is the gene most relevant to immune cells and function in CC. Our study conducted a comprehensive and systematic analysis of m7G-associated miRNAs to construct prognostic profiles of CC. We developed a prognostic risk model based on m7G-miRNAs, with the resulting risk scores demonstrating considerable potential as prognostic biomarkers. These findings provide substantial evidence for the critical role of m7G-related miRNAs in colon cancer and may offer new immunotherapeutic targets for patients with this disease.
结肠癌（CC）是一种在全球范围内高度流行的恶性肿瘤，其特征是死亡率高且预后不良。N7-甲基鸟苷（m7G）甲基化是一种新兴的RNA修饰类型，与许多肿瘤的发生发展有关。尽管如此，m7G相关的微小RNA（miRNA）与CC之间的相关性仍有待阐明。本研究旨在探讨m7G相关miRNA在预测CC预后和肿瘤微环境（TME）方面的临床意义。我们从一个可公开访问的数据库中检索了转录组数据和相关临床信息。通过单因素Cox和LASSO回归分析，我们建立了一个m7G相关miRNA的特征。此外，我们使用CIBERSORT和ssGSEA算法来探索CC患者预后风险评分与TME之间的关联。通过考虑风险特征和免疫浸润，我们确定了有助于CC预后的差异表达基因。最后，使用定量逆转录聚合酶链反应（qRT-PCR）在细胞系中验证了预后miRNA的表达模式。我们基于7个m7G相关的miRNA（miR-136-5p、miR-6887-3p、miR-195-5p、miR-149-3p、miR-4433a-5p、miR-31-5p和miR-129-2-3p）构建了一个预后风险特征。随后，我们观察到高风险组和低风险组患者的预后存在显著差异。ROC曲线中1年、3年和5年生存率的曲线下面积（AUC）分别为0.735、0.707和0.632。此外，我们的结果表明，风险评分可作为总生存预测的独立预后生物标志物。在免疫分析方面，结果显示风险特征与免疫浸润以及免疫检查点表达之间存在显著关联。最后，我们的研究表明CCDC160和RLN3是CC中与免疫细胞和功能最相关的基因。我们的研究对mG相关的miRNA进行了全面系统的分析，以构建CC的预后图谱。我们基于m7G-miRNA开发了一种预后风险模型，所得风险评分显示出作为预后生物标志物的巨大潜力。这些发现为m7G相关miRNA在结肠癌中的关键作用提供了大量证据，并可能为该疾病患者提供新的免疫治疗靶点。
