摘要: |
目的 探讨结肠癌中 m6A- 脂肪酸代谢相关 lncRNA,并分析其与患者预后及肿瘤免疫微环境的相关性,为结肠癌患者诊治提供新的分子靶点。方法 从 TCGA 数据库中获取结肠癌患者的转录组数据及临床信息。通过 Pearson 相关分析筛选出 m6A- 脂肪酸代谢相关 lncRNA。采用单因素、LASSO 及多因素 Cox 回归分析构建基于 lncRNA 表达的风险模型;通过 Kaplan-Meier 生存曲线、ROC 曲线及列线图验证风险模型的准确性。比较高风险组及低风险组结肠癌患者免疫细胞浸润情况。结果 从 TCGA 数据库中鉴定出 670 个 m6A 相关 lncRNA 及 1 011 个脂肪酸代谢相关 lncRNA,其中 39 个交叉的lncRNA 具有预后意义。通过 LASSO 及多因素回归构建了包含 5 个 m6A- 脂肪酸代谢相关 lncRNA 的风险模型,风险评分较高者预后较差。多因素 Cox 回归分析表明风险评分是影响患者预后的独立相关因素(HR=11.8, 95%CI 3.6~38.7)。ROC曲线显示其预测患者 1 年、3 年、5 年生存率的曲线下面积分别为 0.758 (95%CI 0.611~0.905)、0.793 (95%CI 0.708~0.877)和 0.815 (95%CI 0.722~0.907)。相较于高风险组,低风险组肿瘤有更多的 M1 型巨噬细胞浸润(P<0.05),免疫检查点基因(CD44、TNFRSF9、CD40LG、CD48、CD244、IDO1、HAVCR2、CD27、ICOS、LAIR1、TMIGD2、CD28、TIGIT)表达增高(P<0.05)。结论 该 m6A- 脂肪酸代谢相关 lncRNA 风险模型可用于预测结肠癌患者预后及免疫疗效。 |
关键词: 结肠癌 m6A 脂肪酸代谢 lncRNA 免疫治疗 |
DOI:10.12025/j.issn.1008-6358.2024.20231786 |
分类号:R 735.3 |
基金项目:国家自然科学基金(82103246),上海市青年科技英才扬帆计划(21YF1425900). |
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Predictive values of m6A-fatty-acid-metabolism-related lncRNA in prognosis and immune efficiency of colon cancer |
SHEN Chaoqin, LIU Taotao
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Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Abstract: |
Objective To explore the m6A-fatty-acid-metabolism-related lncRNAs in colon cancer, and to analyze their correlation with colon cancer prognosis and tumor immune microenvironment, thus providing new molecular targets for diagnosis and treatment of colon cancer patients. Methods Transcriptome data and relevant clinical information of colon cancer patients were downloaded from TCGA database. m6A-fatty-acid-metabolism-related lncRNAs were identified through Pearson correlation analysis. The risk model based on lncRNA expression was established using univariate Cox regression analysis, LASSO regression analysis, and multivariate Cox regression analysis. The validity of the prognostic risk model was verified using Kaplan-Meier survival analysis, ROC curve, and nomogram. The immune cell infiltration was compared between high-risk and low-risk groups. Results 670 m6A-related lncRNAs and 1 011 fatty-acid-metabolism-related lncRNAs were identified from TCGA, and 39 lncRNAs of their intersection had prognostic significance. A risk model containing 5 lncRNAs related to m6A modification and fatty acid metabolism was established using LASSO and multivariate Cox regression analysis. Colon cancer patients with higher risk scores were more likely to have a worse prognosis than those with lower risk scores. Multivariate Cox regression analysis indicated that the risk score was an independent prognostic factor for colon cancer (HR=11.8, 95%CI 3.6-38.7). ROC analysis manifested that the area under curve (AUC) of the model predicting survival rate at 1, 3 and 5 years were 0.758 (95%CI 0.611-0.905), 0.793 (95%CI 0.708- 0.877) and 0.815 (95%CI 0.722-0.907). Compared with the high-risk group, the low-risk group had increased M1 macrophages (P<0.05) and higher expression of immune checkpoints (CD44, TNFRSF9, CD40LG, CD48, CD244, IDO1, HAVCR2, CD27, ICOS, LAIR1, TMIGD2, CD28 and TIGIT; P<0.05). Conclusions This m6A-fatty-acid-metabolism-related lncRNA risk model could be used to predict prognosis and immunotherapy response of colon cancer patients. |
Key words: colon cancer m6A long non-coding RNA fatty acid metabolism immunotherapy |