Ma Bin, Bao Simeng, Li Yongmin
Department of Colorectal Surgery, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang, China.
The Liaoning Provincial Key Laboratory of Interdisciplinary Research on Gastrointestinal Tumor Combining Medicine with Engineering, Shenyang, China.
Front Oncol. 2023 Jun 23;13:1145753. doi: 10.3389/fonc.2023.1145753. eCollection 2023.
In order to develop an N6-methyladenosine-related gene prognostic index (m6A-GPI) that can predict the prognosis in colorectal cancer (CRC), we obtained m6A-related differentially expressed genes (DEGs) based on The Cancer Genome Atlas (TCGA) and m6Avar database, seven genes were screened by weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) analysis. Then, m6A-GPI was constructed based on the risk score. Survival analysis indicated that patients in the lower m6A-GPI group have more prolonged disease-free survival (DFS), and different clinical characteristic groups (tumor site and stage) also showed differential risk scores. In the analysis of the molecular characteristics, the risk score is positively associated with homologous recombination defects (HRD), copy number alterations (CNA), and the mRNA expression-based stemness index (mRNAsi). In addition, m6A-GPI also plays an essential role in tumor immune cell infiltration. The immune cell infiltration in the low m6A-GPI group is significantly higher in CRC. Moreover, we found that CIITA, one of the genes in m6A-GPI was up-regulated in CRC tissues based on real-time RT-PCR and Western blot. m6A-GPI is a promising prognostic biomarker that can be used to distinguish the prognosis of CRC patients in CRC.
为了开发一种能够预测结直肠癌（CRC）预后的N6-甲基腺苷相关基因预后指数（m6A-GPI），我们基于癌症基因组图谱（TCGA）和m6Avar数据库获得了m6A相关的差异表达基因（DEGs），通过加权基因共表达网络分析（WGCNA）和最小绝对收缩和选择算子（LASSO）分析筛选出7个基因。然后，基于风险评分构建m6A-GPI。生存分析表明，m6A-GPI较低组的患者无病生存期（DFS）更长，不同临床特征组（肿瘤部位和分期）的风险评分也存在差异。在分子特征分析中，风险评分与同源重组缺陷（HRD）、拷贝数改变（CNA）以及基于mRNA表达的干性指数（mRNAsi）呈正相关。此外，m6A-GPI在肿瘤免疫细胞浸润中也起着重要作用。CRC中m6A-GPI较低组的免疫细胞浸润明显更高。此外，基于实时RT-PCR和蛋白质免疫印迹，我们发现m6A-GPI中的一个基因CIITA在CRC组织中上调。m6A-GPI是一种有前景的预后生物标志物，可用于区分CRC患者的预后。
