首页|基于乳酸代谢基因的软组织肉瘤预后模型的建立及评价

基于乳酸代谢基因的软组织肉瘤预后模型的建立及评价

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目的 在软组织肉瘤中建立乳酸代谢相关基因的风险评分模型,并分析其与肿瘤突变负荷及肿瘤微环境中免疫细胞、免疫功能和免疫检查点的相关性.方法 通过TCGA和GTEx数据库中获取软组织肉瘤的差异表达基因,再结合分子标签数据库(Msigdb)中乳酸代谢相关基因集获取软组织肉瘤中乳酸代谢相关的差异表达基因,并进行基因本体、京都基因与基因组百科全书通路富集分析;通过单因素比例风险模型和最小绝对收缩和选择算子回归构建风险评分模型,将软组织肉瘤样本分为高风险组和低风险组;最后,分析2组之间的肿瘤突变负荷、肿瘤微环境免疫状态.结果 共筛选出29个与乳酸代谢相关的差异表达基因.通路富集分析结果表明,这29个基因主要与代谢过程有关.构建预后风险评分模型,按风险评分中位值将软组织肉瘤样本分为高风险组和低风险组,肿瘤突变负荷分析结果显示,在所有软组织肉瘤样本中,首位突变基因均为肿瘤蛋白p53.最常见的体细胞突变类型是错义突变,且高风险组中的基因突变频率比低风险组高.肿瘤微环境分析结果表明,高风险组中 M0、M2型巨噬细胞浸润多,而在低风险组中CD8+T细胞和单核细胞浸润比例较高.低风险组中免疫相关功能反应、免疫检查点表达比高风险组高.结论 乳酸代谢评分模型可以较好地评估软组织肉瘤患者的预后及反映肿瘤微环境的状态.
Establishment and evaluation of a prognosis model of soft tissue sarcoma based on lactic acid metabolism gene
Objective To establish a risk model for lactate metabolism-related genes in soft tissue sarcomas,and to explore their correlation with tumor mutational burden,immune cells,immune related functions and immune checkpoints in the tumor microenvironment.Methods The differentially expressed genes associated with lactate metabolism in soft tissue sarcoma were obtained after intersecting the differentially expressed genes extracted by TCGA and GTEx database with lactate metabolism-related gene sets from the Msigdb database.The pathway enrichment analysis was carried out by gene ontology and Kyoto Encyclopedia of Genes and Genomes.By the univariate Cox regression and least absolute shrinkage and selection operator to construct a risk score model,and divided the soft tissue sarcomas samples into high-risk and low-risk groups.Finally,the differences of the tumor mutational burden and immunity in the tumor microenvironment between the two groups were analyzed.Results A total of 29 differentially expressed genes associated with lactate metabolism were screened,and the results of pathways enrichment analysis showed that they were mainly related to metabolic processes.By constructing a predictive risk score model,soft tissue sarcoma samples were divided into high-risk and low-risk groups.Tumor mutational burden analysis showed that the first mutated gene was tumor protein p53 in all soft tissue sarcoma samples.Missense mutation was the most common type of somatic mutations,and the frequency of mutation was higher in the high-risk group than that in the low-risk group.The analysis of tumor microenvironment indicated that the infiltration of M0 and M2 macrophage was more in the high-risk group,while the low-risk group had a higher percentage of infiltrating CD8+T cells and monocytes.The immune related functional response and immune checkpoints expression was higher in the low-risk group.Conclusion The lactate metabolism scoring model can better evaluate the prognosis of patients with soft tissue sarcoma and reflect the state of tumor microenvironment.

soft tissue sarcomalactate metabolismmodel specificationtumor mutational burdentumor microenvironment

张田田、孟莲、孙皓、刘春霞

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石河子大学医学院病理学系,新疆维吾尔自治区石河子 832002

广州医科大学附属第二医院病理科,广东广州 510260

软组织肉瘤 乳酸代谢 模型构建 肿瘤突变负荷 肿瘤微环境

国家自然科学基金资助项目国家自然科学基金资助项目广州市科技计划市校联合基金资助项目

8196048582060487202201020104

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(13)
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