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基于免疫基因组图谱分析的前列腺癌预后标志物的开发与验证

Development and Verification of a Prostate Cancer Prognostic Signature Based on an Immunogenomic Landscape Analysis.

作者信息

Cheng Hong, Wang Yi, Liu Chunhui, Wu Tiange, Chen Shuqiu, Chen Ming

机构信息

Department of Urology, Zhongda Hospital Affiliated to Southestern China University, Nanjing, China.

Department of Urology, Affiliated Hospital of Nantong University, Nantong, China.

出版信息

Front Oncol. 2021 Sep 9;11:711258. doi: 10.3389/fonc.2021.711258. eCollection 2021.

DOI:10.3389/fonc.2021.711258
PMID:34568039
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8459614/
Abstract

PURPOSE

Prostate cancer (PCa) has a high incidence among older men. Until now, there are no immunological markers available to predict PCa patients' survival. Therefore, it is necessary to explore the immunological characteristics of PCa.

METHODS

First, we retrieved RNA-seq and clinical data of 499 PCa and 52 normal prostate tissue samples from the Cancer Genome Atlas (TCGA). We identified 193 differentially expressed immune-related genes (IRGs) between PCa and normal prostate tissues. Functional enrichment analyses showed that the immune system can participate in PCa initiation. Then, we constructed a correlation network between transcription factors (TFs) and IRGs. We performed univariate and multivariate Cox regression analyses and identified five key prognostic IRGs (S100A2, NOX1, IGHV7-81, AMH, and AGTR1). Finally, a predictive nomogram was established and verified by the C-index.

RESULTS

We successfully constructed and validated an immune-related PCa prediction model. The signature could independently predict PCa patients' survival. Results showed that high-immune-risk patients were correlated with advanced stage. We also validated the S100A2 expression using PCa and normal prostate tissues. We found that higher S100A2 expressions were related to lower biochemical recurrences. Additionally, higher AMH expressions were related to higher Gleason score, lymph node metastasis and positive rate, and tumor stages, and higher ATGR1 expressions were related to lower PSA value.

CONCLUSION

Overall, we detected five IRGs (S100A2, NOX1, IGHV7-81, AMH, and AGTR1) that can be used as independent PCa prognostic factors.

摘要

目的

前列腺癌(PCa)在老年男性中发病率较高。迄今为止,尚无免疫标志物可用于预测PCa患者的生存情况。因此,有必要探索PCa的免疫特征。

方法

首先,我们从癌症基因组图谱(TCGA)中检索了499例PCa和52例正常前列腺组织样本的RNA测序和临床数据。我们鉴定出PCa与正常前列腺组织之间193个差异表达的免疫相关基因(IRGs)。功能富集分析表明,免疫系统可参与PCa的起始过程。然后,我们构建了转录因子(TFs)与IRGs之间的关联网络。我们进行了单变量和多变量Cox回归分析,并确定了五个关键的预后IRGs(S100A2、NOX1、IGHV7-81、AMH和AGTR1)。最后,建立了一个预测列线图,并通过C指数进行验证。

结果

我们成功构建并验证了一个与免疫相关的PCa预测模型。该特征可独立预测PCa患者的生存情况。结果表明,高免疫风险患者与晚期相关。我们还使用PCa和正常前列腺组织验证了S100A2的表达。我们发现较高的S100A2表达与较低的生化复发相关。此外,较高的AMH表达与较高的Gleason评分、淋巴结转移及阳性率和肿瘤分期相关,而较高的ATGR1表达与较低的PSA值相关。

结论

总体而言,我们检测到五个IRGs(S100A2、NOX1、IGHV7-81、AMH和AGTR1)可作为独立的PCa预后因素。

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