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开发一种新的基于免疫浸润的基因特征,以预测宫颈癌患者的预后和免疫治疗反应。

Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer.

机构信息

Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Front Immunol. 2021 Sep 3;12:709493. doi: 10.3389/fimmu.2021.709493. eCollection 2021.

Abstract

Predictive models could indicate the clinical outcome of patients with carcinoma. Cervical cancer is one of the most frequently diagnosed female malignancies. Herein, we proposed an immune infiltration-related gene signature that predicts prognosis of patients with cervical cancer and depicts the immune landscape as well. We utilized the transcriptome data of The Cancer Genome Atlas (TCGA) and estimated the infiltration level of 28 immune cell types. We screened out four immune cell types conducive to patient survival and recognized their shared differentially expressed genes (DEGs). Four core genes (CHIT1, GTSF1L, PLA2G2D, and GNG8) that composed the ultimate signature were identified univariate and multivariate Cox regression. The optimal model we built up could distinguish patients with cervical cancer into high-score and low-score subgroups. These two subgroups showed disparity in aspects of patient survival, immune infiltration landscape, and response to immune checkpoint inhibitors. Additionally, we found that GTSF1L was decreased gradually along with the severity of cervical lesions, and its potential role in immune contexture and clinical practice were also demonstrated. Our results suggested that the Immunoscore based on four immune-related genes could serve as a supplementary criterion to effectively foresee the survival outcome, tumor infiltration status, and immunotherapy efficacy of cervical cancer patients.

摘要

预测模型可以指示癌症患者的临床预后。宫颈癌是最常见的女性恶性肿瘤之一。在此,我们提出了一个与免疫浸润相关的基因特征,用于预测宫颈癌患者的预后,并描绘了免疫图谱。我们利用癌症基因组图谱 (TCGA) 的转录组数据,并估计了 28 种免疫细胞类型的浸润水平。我们筛选出有利于患者生存的四种免疫细胞类型,并识别出它们的共同差异表达基因 (DEGs)。四个核心基因(CHIT1、GTSF1L、PLA2G2D 和 GNG8)构成了最终的特征,通过单变量和多变量 Cox 回归进行鉴定。我们建立的最优模型可以将宫颈癌患者分为高分和低分亚组。这两个亚组在患者生存、免疫浸润景观以及对免疫检查点抑制剂的反应方面存在差异。此外,我们发现 GTSF1L 随着宫颈病变的严重程度逐渐降低,并且其在免疫结构和临床实践中的潜在作用也得到了证明。我们的研究结果表明,基于四个免疫相关基因的免疫评分可以作为一种辅助标准,有效预测宫颈癌患者的生存结果、肿瘤浸润状态和免疫治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a817/8446628/ae745d75019a/fimmu-12-709493-g001.jpg

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