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免疫细胞浸润的两步共识聚类方法:肉瘤预后和免疫影响的综合探索与验证

Two-step consensus clustering approach to immune cell infiltration: An integrated exploration and validation of prognostic and immune implications in sarcomas.

作者信息

Li Ao-Yu, Bu Jie, Xiao Hui-Ni, Zhao Zi-Yue, Zhang Jia-Lin, Yu Bin, Li Hui, Li Jin-Ping, Xiao Tao

机构信息

Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, China.

Orthopedic Biomedical Materials Engineering Laboratory of Hunan Province, Changsha, China.

出版信息

Heliyon. 2024 Oct 1;10(20):e38253. doi: 10.1016/j.heliyon.2024.e38253. eCollection 2024 Oct 30.


DOI:10.1016/j.heliyon.2024.e38253
PMID:39492897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11531637/
Abstract

To conduct a comprehensive investigation of the sarcoma immune cell infiltration (ImmCI) patterns and tumoral microenvironment (TME). We utilized transcriptomic, clinical, and mutation data of sarcoma patients (training cohort) obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) server. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithms were applied to decipher the immune cell infiltration landscape and TME profiles of sarcomas. An unsupervised clustering method was utilized for classifying ImmCI clusters (initial clustering) and ImmCI-based differentially expressed gene-driven clusters (secondary clustering). Mortality rates and immune checkpoint gene levels was analyzed among the identified clusters. We calculated the ImmCI score through principal component analysis. The tumor immune dysfunction evaluation (TIDE) score was also employed to quantify immunotherapy efficacy between two ImmCI score groups. We further validated the biomarkers for ImmCI and gene-driven clusters via experimental verification and the accuracy of the ImmCI score in predicting survival outcomes and immunotherapy efficacy by external validation cohorts (testing cohort). We demonstrated that ImmCI cluster A and gene-driven cluster A, were beneficial prognostic biomarkers and indicators of immune checkpoint blockade response in sarcomas via and laboratory experiments. Additionally, the ImmCI score exhibited independent prognostic significance and was predictive of immunotherapy response. Our research underscores the clinical significance of ImmCI scores in identifying sarcoma patients likely to respond to immunotherapy.

摘要

为了全面研究肉瘤的免疫细胞浸润(ImmCI)模式和肿瘤微环境(TME)。我们利用了从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)服务器获得的肉瘤患者(训练队列)的转录组学、临床和突变数据。应用通过估计RNA转录本相对子集进行细胞类型鉴定(CIBERSORT)和利用表达数据估计恶性肿瘤组织中的基质和免疫细胞(ESTIMATE)算法来解读肉瘤的免疫细胞浸润格局和TME概况。采用无监督聚类方法对ImmCI簇(初始聚类)和基于ImmCI的差异表达基因驱动簇(二次聚类)进行分类。分析了所识别簇中的死亡率和免疫检查点基因水平。我们通过主成分分析计算ImmCI评分。还采用肿瘤免疫功能障碍评估(TIDE)评分来量化两个ImmCI评分组之间的免疫治疗疗效。我们通过实验验证进一步验证了ImmCI和基因驱动簇的生物标志物,并通过外部验证队列(测试队列)验证了ImmCI评分在预测生存结果和免疫治疗疗效方面的准确性。我们通过临床和实验室实验证明,ImmCI簇A和基因驱动簇A是肉瘤中有益的预后生物标志物和免疫检查点阻断反应的指标。此外,ImmCI评分具有独立的预后意义,并可预测免疫治疗反应。我们的研究强调了ImmCI评分在识别可能对免疫治疗有反应的肉瘤患者中的临床意义。

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Two-step consensus clustering approach to immune cell infiltration: An integrated exploration and validation of prognostic and immune implications in sarcomas.

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本文引用的文献

[1]
Comprehensive Immune Profiling Unveils a Subset of Leiomyosarcoma with "Hot" Tumor Immune Microenvironment.

Cancers (Basel). 2023-7-21

[2]
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Front Pharmacol. 2023-3-1

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PD-L1 tumour expression is predictive of pazopanib response in soft tissue sarcoma.

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