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免疫微环境分类与 12 种细胞死亡方式相关,并构建了鳞状细胞肺癌的预后模型。

Classification of the immune microenvironment associated with 12 cell death modes and construction of a prognostic model for squamous cell lung cancer.

机构信息

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

出版信息

J Cancer Res Clin Oncol. 2023 Sep;149(11):9051-9070. doi: 10.1007/s00432-023-04789-w. Epub 2023 May 12.

Abstract

PURPOSE

An increasing number of patients with lung squamous cell carcinoma (LUSC) are benefiting from immunotherapy. However, the individual immune profile of patients who respond to treatment is unclear. Multiple programmed cell death (PCD) patterns play an important role in the proliferation and differentiation of tumor cells, predicting the efficacy of immunotherapy using a risk model for programmed cell death gene combinations LUSC risk model.

METHODS

Genes associated with 12 types of PCD were analyzed to establish a prognostic model. Risk scores were calculated using PCDG-based expression profiles, and LUSC patients were classified into two groups. Tumor immune microenvironment (TIME) characteristics and immunotherapy responses were compared between the two groups. Finally, staging was predicted using the extreme gradient boosting tree algorithm (eXtreme Gradient Boosting, XGBoost), and an algorithmic model was constructed to predict the prognosis of LUSC patients based on the PCDG risk score.

RESULTS

A stepwise downscaling of 1256 PCDGs was performed to screen out 16 genes associated with LUSC prognosis to construct a risk model. Immune cell infiltration levels, the immunotherapy response, and prognostic differences were different between these two groups of patients. The classification prediction model based on the XGBoost algorithm and the prognostic model based on the risk score were able to distinguish the risk subtypes and individual prognosis of LUSC patients, respectively.

CONCLUSIONS

PCD patterns exert a crucial effect on the development of LUSC. An evaluation of different PCD patterns in LUSC improves the understanding of the characteristics of infiltrating immune cells and mutational features of the TIME, distinguishes LUSC patients who might benefit from immunotherapy, and predicts their future survival.

摘要

目的

越来越多的肺鳞状细胞癌(LUSC)患者从免疫治疗中获益。然而,对于治疗反应的患者的个体免疫特征尚不清楚。多种程序性细胞死亡(PCD)模式在肿瘤细胞的增殖和分化中发挥重要作用,使用程序性细胞死亡基因组合 LUSC 风险模型预测免疫治疗的疗效。

方法

分析与 12 种 PCD 相关的基因,建立预后模型。使用基于 PCDG 的表达谱计算风险评分,并将 LUSC 患者分为两组。比较两组患者的肿瘤免疫微环境(TIME)特征和免疫治疗反应。最后,使用极端梯度提升树算法(极端梯度提升,XGBoost)进行分期预测,并构建基于 PCDG 风险评分预测 LUSC 患者预后的算法模型。

结果

对 1256 个 PCDG 进行逐步降维,筛选出与 LUSC 预后相关的 16 个基因构建风险模型。两组患者的免疫细胞浸润水平、免疫治疗反应和预后差异不同。基于 XGBoost 算法的分类预测模型和基于风险评分的预后模型能够分别区分 LUSC 患者的风险亚型和个体预后。

结论

PCD 模式对 LUSC 的发展有重要影响。评估 LUSC 中不同的 PCD 模式可提高对浸润免疫细胞特征和 TIME 突变特征的认识,区分可能受益于免疫治疗的 LUSC 患者,并预测其未来生存。

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