m5C/m6A/m7G相关非凋亡调节细胞死亡基因用于预测肝细胞癌的预后和免疫浸润状态。
The m5C/m6A/m7G-related non-apoptotic regulatory cell death genes for the prediction of the prognosis and immune infiltration status in hepatocellular carcinoma.
发表日期:2024 Sep 30
作者:
Xiangyu Qu, Yigang Zhang, Haoling Li, Yi Tan
来源:
Cell Death & Disease
摘要:
5-甲基胞嘧啶/N6-甲基腺苷/N7-甲基鸟苷(m5C/m6A/m7G)相关基因在肿瘤的发生和进展中发挥着关键作用,非凋亡调节性细胞死亡(NARCD)与肿瘤的发生和免疫密切相关。然而,m5C/m6A/m7G 相关 NARCD 基因在肝细胞癌 (HCC) 中的作用仍不清楚。我们利用m5C/m6A/m7G相关的NARCD基因构建了HCC的预后模型,用于患者的预后预测和临床治疗。我们从癌症基因组图谱(TCGA)和国际癌症基因组联盟(ICGC)获得了HCC的转录组数据。使用最小绝对收缩和选择算子(LASSO)回归,我们鉴定了 m5C/m6A/m7G 相关的 NARCD 基因,并通过多元 Cox 回归构建了预后模型。使用 Kaplan-Meier 和受试者工作特征 (ROC) 曲线评估模型性能,并使用 ICGC 进行外部验证。使用京都基因和基因组百科全书(KEGG)和基因本体论(GO)分析来研究高风险组和低风险组之间的差异表达基因。我们还检查了高危人群中的免疫细胞浸润、药物反应以及肿瘤细胞与免疫细胞之间的细胞通讯。我们鉴定了 140 个 m5C/m6A/m7G 相关 NARCD 基因,并使用其中的 5 个构建了预后模型。功能富集分析揭示了风险基因在肿瘤和免疫相关通路中的富集。高风险组表现出免疫细胞浸润增加和对免疫检查点抑制剂(ICIs)的更好反应。高风险患者对顺铂、阿霉素和丝裂霉素 C 更敏感,而低风险患者对厄洛替尼更敏感。细胞通讯分析表明,高危肿瘤细胞利用胰岛素样生长因子(IGF)和巨噬细胞迁移抑制因子(MIF)信号通路向免疫细胞发送信号,并通过骨形态发生蛋白(BMP)和淋巴毒素相关蛋白接收信号。诱导配体(LIGHT)途径。我们开发了一种具有 m5C/m6A/m7G 相关 NARCD 基因的预后模型来预测 HCC 患者的预后。该模型可以深入了解 HCC 患者免疫治疗和化疗的有效性。2024 AME 出版公司。版权所有。
5-methylcytosine/N6-methyladenosine/N7-methylguanosine (m5C/m6A/m7G)-related genes play a critical role in tumor occurrence and progression, and non-apoptotic regulatory cell death (NARCD) is closely linked to tumor development and immunity. However, the role of m5C/m6A/m7G-related NARCD genes in hepatocellular carcinoma (HCC) remains unclear. We used m5C/m6A/m7G-related NARCD genes to construct a prognostic model of HCC for prognostic prediction and clinical treatment of patients.We obtained transcriptome data for HCC from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Using the least absolute shrinkage and selection operator (LASSO) regression, we identified m5C/m6A/m7G-related NARCD genes and constructed a prognostic model through multivariate Cox regression. Model performance was assessed using Kaplan-Meier and receiver operating characteristic (ROC) curves, with external validation using the ICGC. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were used to study differentially expressed genes between high- and low-risk groups. We also examined immune cell infiltration, drug response, and cell communication between tumor cells and immune cells in high-risk groups.We identified 140 m5C/m6A/m7G-related NARCD genes, using five of them to build the prognostic model. Functional enrichment analysis revealed enrichment in tumor and immune-related pathways for risk genes. The high-risk group displayed increased immune cell infiltration and better responses to immune checkpoint inhibitors (ICIs). High-risk patients were more responsive to cisplatin, doxorubicin, and mitomycin C, while low-risk patients were more sensitive to erlotinib. Cell communication analysis indicated that high-risk tumor cells used insulin-like growth factor (IGF) and macrophage migration inhibitory factor (MIF) signaling pathways to send signals to immune cells and received signals through the bone morphogenetic protein (BMP) and lymphotoxin-related inducible ligand (LIGHT) pathways.We have developed a prognostic model with m5C/m6A/m7G-related NARCD genes to predict the prognosis of HCC patients. This model can offer insights into the effectiveness of immunotherapy and chemotherapy for HCC patients.2024 AME Publishing Company. All rights reserved.