医学分子生物学杂志 ›› 2025, Vol. 22 ›› Issue (5): 442-451.doi: 10.3870/j.issn.1672-8009.2025.05.005

• 论著 • 上一篇    下一篇

基于生物信息学分析乳酸代谢基因对肺鳞癌预后及免疫微环境的影响 #br#

  

  1. 1华中科技大学同济医学院基础医学院 武汉市, 430030 2华中科技大学同济医学院附属协和医院呼吸与危重症医学科 武汉市, 430022
  • 出版日期:2025-09-30 发布日期:2025-10-09
  • 基金资助:
    国家重点研发项目(No. 2023YFC0872500),国家自然科学基金( No. 82270110),湖北省重点研发计划项目( No. 2023BCB146),京山联合面上项目(No. 2023-XHJS-029)

Effect of Lactic Acid Metabolism Genes on Prognosis of Lung Squamous Cell Carcinoma and Immune Microenvironment Based on Bioinformatics Analysis #br#

  1. 1School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China 2Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
  • Online:2025-09-30 Published:2025-10-09

摘要: 目的 以生物信息学的分析方法探究乳酸代谢基因在肺鳞癌 ( lung squamous cell carcinoma,LUSC) 中的表达情况, 分析其对于 LUSC 预后及免疫微环境的影响方法 通过分析癌症基因图谱数据库(TCGA) 和高通量基因表达数据库 (GEO) 中的 LUSC 相关的乳酸代谢基因; 通过单因素 Cox 回归、 LASSO 回归和多因素 Cox 回归分析筛选出生存相关乳酸代谢基因并以此构建 LUSC 的预后模型; 使用 CIBERSORT 方法评估该风险分组中患者基因表达图谱与免疫细胞浸润情况的关系; 采用 Kaplan-Meier ( KM) 生存分析和受试者工作特征 (ROC) 在内部训练队列和外部验证队列分别验证模型的预测能力; 综合风险分组和临床信息得出患者生存时间得分列线图结果 成功筛选出 34 个生存相关乳酸代谢基因并构建 LUSC患者 1、 3、 5 年预后模型, 根据乳酸代谢基因表达量得出风险评分, LUSC 患者分为高风险组和低风险组, 其中风险分组与 LUSC 免疫微环境中静息 CD4 + 记忆 T 细胞 (P = 0. 001)、 活化 CD4 + 记忆 T 细胞 (P< 0. 001)、 静息 NK 细胞 (P = 0. 03)、 单核细胞 (P = 0. 01)、 M0 型巨噬细胞 (P = 0. 009)、 活化树突状细胞(P< 0. 001)、 活化肥大细胞 (P = 0. 04) 和中性粒细胞 (P< 0. 001) 的浸润丰度相关。 KM 生存分析表明低风险组总生存时间明显高于高风险组 ( P< 0. 001)。 风险评分预测 LUSC 患者 1、 3、 5 ROC 曲线下面积(AUC) > 0. 7, 联合风险分组与临床信息后得到可预测患者 1、 3、 5 年生存率的列线图, 校正曲线显示预测准确率较好结论 乳酸代谢基因可用于构建 LUSC 预后模型, 其构建的风险评分可用于评估 LUSC 患者的免疫微环境及 1、 3、 5 年预后情况

关键词: 肺鳞癌, 预后模型, 免疫微环境, 乳酸代谢, 生物信息学

Abstract: Objective To screen out differentially expressed lactic acid metabolism genes inlung squamous cell carcinoma (LUSC), and to investigate their influence on LUSC prognosis andimmune microenvironment through bioinformatics analysis. Methods RNA sequencing and clinicaldata were obtained from public databases. Differentially expressed lactic acid metabolism genes in LUSC and normal tissues were identified by integrated bioinformatics analysis. Univariate Cox, LASSO and multivariate Cox regression analyses were applied to screen out survival-associated lactic acid metabolism genes. CIBERSORT was used to evaluate the relationship between gene expression atlas and immune cell infiltration in patients of different risk groups. Kaplan-Meier (KM) survival analysis and receiver operating characteristics ( ROC) were used to verify the predictive power of the model in an internal training cohort and an external validation cohort, respectively. Risk groups and clinical information were combined to produce a nomogram to predict the survival time of LUSC patients. Results A total of 34 survival-associated lactic acid metabolism genes were successfullyscreened out, and prognosis models were constructed based on these genes. According to this model, LUSC patients were divided into a high-risk group and a low-risk group. Resting CD4 + memoryT cells ( P = 0. 001), activated CD4 + memory T cells ( P < 0. 001), resting NK cells ( P =0. 03), monocytes (P = 0. 01), M0 macrophages (P = 0. 009), activated dendritic cells (P <0. 001), active mast cells (P = 0. 04) and neutrophils (P< 0. 001) in LUSC immune microenvironment were associated with risk groups. KM survival analysis showed that the total survival time ofthe low-risk group was significantly longer than that of the high-risk group (P< 0. 001). The areasunder the ROC curve (AUC) of LUSC patients at 1, 3 and 5 years were all larger than 0. 7. Aftercombining risk groups and clinical information, a nomogram was obtained that could predict the survival rate of LUSC patients at 1, 3 and 5 years, and the correction curve showed a good predictionaccuracy. Conclusion LUSC prognosis model and its risk groups constructed by 34 lactic acid metabolism genes can be used to evaluate the immune microenvironment and the survival rate of LUSCpatients at 1, 3 and 5 years.

Key words:

lung squamous cell carcinoma, prognosis model, immune microenvironment, lactic acid metabolism, bioinformatics

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