Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, 20 Xisi Street, Nantong, 226001, Jiangsu, China.
Graduate School of Dalian Medical University, No.9 West Section of South Lushun Road, Dalian, 116000, Liaoning, China.
Sci Rep. 2022 Dec 8;12(1):21282. doi: 10.1038/s41598-022-25823-w.
N7-methyladenosine (mG) modifications have been the subject of growing research interest with respect to their relationship with the progression and treatment of various cancers. This analysis was designed to examine the association between mG-related gene expression and colorectal cancer (CRC) patient outcomes. Initial training analyses were performed using the TCGA dataset, with the GSE28722 dataset then being used to validate these results. Univariate Cox analyses were initially conducted to screen out prognostic mG-related genes, after which a LASSO approach was used to construct an mG risk score (MRS) model. Kaplan-Meier curves, ROC curves, and Cox analyses were subsequently used to validate the prognostic utility of this model in CRC patients. The R maftools package was further employed to assess mutational characteristics in CRC patients in different MRS subgroups, while the ESTIMATE, CIBERSORT, and ssGSEA tools were used to conduct immune infiltration analyses. A WGCNA was then performed to identify key immune-associated hub genes. The EIF4E3, GEMIN5, and NCBP2 genes were used to establish the MRS model. Patients with high MRS scores exhibited worse overall survival than patients with low scores. In Cox analyses, MRS scores were independently associated with CRC patient prognosis. Patients with low MRS scores exhibited a higher tumor mutational burden and higher levels of microsatellite instability. In immune infiltration analyses, higher immune checkpoint expression and greater immune cell infiltration were also observed in patients with low MRS scores. WGCNA analyses further identified 25 CD8+ T cell infiltration-associated genes. These findings suggest that MRS values represent a useful biomarker capable of differentiating among CRC patients with different immunological features and prognostic outcomes, offering an opportunity to better determine which patients are likely to benefit from immune checkpoint inhibitor treatment.
N7-甲基腺苷(mG)修饰已成为研究热点,其与各种癌症的发生和治疗密切相关。本分析旨在探讨 mG 相关基因表达与结直肠癌(CRC)患者结局之间的关系。初步训练分析采用 TCGA 数据集,然后使用 GSE28722 数据集验证这些结果。首先进行单变量 Cox 分析,筛选出预后相关的 mG 基因,然后使用 LASSO 方法构建 mG 风险评分(MRS)模型。随后使用 Kaplan-Meier 曲线、ROC 曲线和 Cox 分析验证该模型在 CRC 患者中的预后预测能力。进一步使用 R maftools 包评估不同 MRS 亚组 CRC 患者的突变特征,使用 ESTIMATE、CIBERSORT 和 ssGSEA 工具进行免疫浸润分析。然后进行 WGCNA 分析,以确定关键的免疫相关枢纽基因。EIF4E3、GEMIN5 和 NCBP2 基因用于构建 MRS 模型。MRS 评分高的患者总生存期较评分低的患者差。Cox 分析表明,MRS 评分与 CRC 患者预后独立相关。MRS 评分低的患者肿瘤突变负担更高,微卫星不稳定性水平更高。免疫浸润分析显示,MRS 评分低的患者免疫检查点表达更高,免疫细胞浸润更多。WGCNA 分析进一步鉴定了 25 个与 CD8+T 细胞浸润相关的基因。这些发现表明,MRS 值是一种有用的生物标志物,可区分具有不同免疫特征和预后结局的 CRC 患者,为更好地确定哪些患者可能受益于免疫检查点抑制剂治疗提供了机会。