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基于自然杀伤细胞的浆液性卵巢癌预后风险模型的建立与验证

Development and Validation of a Prognostic Risk Model Based on Nature Killer Cells for Serous Ovarian Cancer.

作者信息

Zhang Chengxi, Qin Chuanmei, Lin Yi

机构信息

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.

Shanghai Key Laboratory of Embryo Original Diseases, Shanghai 200030, China.

出版信息

J Pers Med. 2023 Feb 24;13(3):403. doi: 10.3390/jpm13030403.

Abstract

Nature killer (NK) cells are increasingly considered important in tumor microenvironment, but their role in predicting the prognosis of ovarian cancer has not been revealed. This study aimed to develop a prognostic risk model for ovarian cancer based on NK cells. Firstly, differentially expressed genes (DEGs) of NK cells were found by single-cell RNA-sequencing dataset analysis. Based on six NK-cell DEGs identified by univariable, Lasso and multivariable Cox regression analyses, a prognostic risk model for serous ovarian cancer was developed in the TCGA cohort. This model was then validated in three external cohorts, and evaluated as an independent prognostic factor by multivariable Cox regression analysis together with clinical characteristics. With the investigation of the underlying mechanism, a relation between a higher risk score of this model and more immune activities in tumor microenvironment was revealed. Furthermore, a detailed inspection of infiltrated immunocytes indicated that not only quantity, but also the functional state of these immunocytes might affect prognostic risk. Additionally, the potential of this model to predict immunotherapeutic response was exhibited by evaluating the functional state of cytotoxic T lymphocytes. To conclude, this study introduced a novel prognostic risk model based on NK-cell DEGs, which might provide assistance for the personalized management of serous ovarian cancer patients.

摘要

自然杀伤(NK)细胞在肿瘤微环境中的重要性日益受到重视,但其在预测卵巢癌预后方面的作用尚未明确。本研究旨在基于NK细胞建立卵巢癌的预后风险模型。首先,通过单细胞RNA测序数据集分析发现NK细胞的差异表达基因(DEG)。基于单变量、Lasso和多变量Cox回归分析确定的6个NK细胞DEG,在TCGA队列中建立了浆液性卵巢癌的预后风险模型。然后在三个外部队列中对该模型进行验证,并通过多变量Cox回归分析结合临床特征将其评估为独立的预后因素。通过对潜在机制的研究,揭示了该模型较高的风险评分与肿瘤微环境中更多免疫活性之间的关系。此外,对浸润免疫细胞的详细检查表明,这些免疫细胞的数量和功能状态都可能影响预后风险。此外,通过评估细胞毒性T淋巴细胞的功能状态,展示了该模型预测免疫治疗反应的潜力。总之,本研究引入了一种基于NK细胞DEG的新型预后风险模型,可为浆液性卵巢癌患者的个性化管理提供帮助。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e57c/10055736/0421f1185b4c/jpm-13-00403-g001.jpg

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