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一种源自肿瘤浸润 T 细胞和中性粒细胞的新型 6 基因标志物可预测膀胱癌患者的生存情况。

A novel 6-gene signature derived from tumor-infiltrating T cells and neutrophils predicts survival of bladder urothelial carcinoma.

机构信息

Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

出版信息

Aging (Albany NY). 2021 Dec 14;13(23):25496-25517. doi: 10.18632/aging.203770.

Abstract

Intratumoral immune cells were reported to be associated with prognosis of bladder urothelial carcinoma (BUC). However, the role of immune cells related genes in BUC prognosis is less well defined. In the study, we analyzed data retrieved from the Cancer Genome Atlas database and found higher neutrophils and lower T cells infiltration in BUC tumor tissues were significantly correlated with patients' worse prognosis. Additionally, the expression levels of 164 genes were significantly correlated with T cells and neutrophils proportions. A Cox proportional-hazards model integrating 6 genes expression (EMP1, RASGRP4, HSPA1L, AHNAK, SLC1A6, and PRSS8) was identified. The 6-gene signature outperformed other clinical factors in risk prediction and was an independent prognostic factor for BUC. The findings were further conformed in three Gene Expression Omnibus datasets (n=331) and Jiangsu Province Hospital cohort (n = 46). Gene set enrichment analysis revealed that the model was highly involved in some immune-related pathways. A comprehensive nomogram combining the model and other clinical parameters was finally constructed to facilitate clinical application. In conclusion, a T cell and neutrophil-associated 6-gene prognostic model was identified for the survival prediction of BUC patients.

摘要

肿瘤内免疫细胞与膀胱癌(BUC)的预后相关。然而,免疫细胞相关基因在 BUC 预后中的作用尚不清楚。在这项研究中,我们分析了从癌症基因组图谱数据库中检索到的数据,发现 BUC 肿瘤组织中中性粒细胞增多和 T 细胞浸润减少与患者预后不良显著相关。此外,164 个基因的表达水平与 T 细胞和中性粒细胞比例显著相关。我们构建了一个包含 6 个基因(EMP1、RASGRP4、HSPA1L、AHNAK、SLC1A6 和 PRSS8)的 Cox 比例风险模型。该 6 基因signature 在风险预测方面优于其他临床因素,是 BUC 的独立预后因素。这一发现在三个基因表达综合数据集(n=331)和江苏省人民医院队列(n=46)中得到了进一步证实。基因集富集分析表明,该模型高度参与了一些免疫相关通路。最后,构建了一个包含模型和其他临床参数的综合列线图,以方便临床应用。总之,我们确定了一个与 T 细胞和中性粒细胞相关的 6 基因预后模型,可用于预测 BUC 患者的生存情况。

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