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促性腺激素释放激素1(GNRH1)和白三烯B4受体(LTB4R)可能是透明细胞肾细胞癌(ccRCC)中与免疫相关的新型预后生物标志物。

GNRH1 and LTB4R might be novel immune-related prognostic biomarkers in clear cell renal cell carcinoma (ccRCC).

作者信息

Wu Hua-Hui, Yan Xin, Chen Zhao, Du Guo-Wei, Bai Xiao-Jie, Tuoheti Kurerban, Liu Tong-Zu

机构信息

Department of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, China.

出版信息

Cancer Cell Int. 2021 Jul 6;21(1):354. doi: 10.1186/s12935-021-02052-1.

DOI:10.1186/s12935-021-02052-1
PMID:34229684
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8259034/
Abstract

BACKGROUND

Clear cell renal cell carcinoma (ccRCC) occupied most of renal cell carcinoma (RCC), which associated with poor prognosis. The purpose of this study is to screen novel and prognostic biomarkers for patients with ccRCC.

METHODS AND RESULTS

Firstly, Gene Expression Omnibus database was used to collect microarray data for weighted gene co-expression network construction. Gene modules related to prognosis which interest us most were picked out. 90 hub genes were further chosen in the key modules, two of which including gonadotropin releasing hormone 1 (GNRH1) and leukotriene B4 receptor (LTB4R) were screened and validated as immune-related prognostic biomarkers. Based on several public databases and ccRCC tissues collected by ourselves, we performed survival analysis, spearman correlation analysis, receiver operating characteristic (ROC) analysis, quantitative real-time PCR (qRT-PCR), western blotting, immunofluorescence (IF) and immunohistochemistry (IHC) staining for the validation of immune-related prognostic biomarkers. We further explored the relationship between immune-related prognostic biomarker expressions and immunocytes. Finally, gene set enrichment analysis (GSEA) demonstrated that the two immune-related prognostic biomarkers were significantly correlated with cell cycle.

CONCLUSIONS

Generally speaking, the present study has identified two novel prognostic biomarkers for patients with ccRCC, which showed strong correlation with prognosis of patients with ccRCC, could further be used as potential prognostic biomarkers in ccRCC.

摘要

背景

透明细胞肾细胞癌(ccRCC)占肾细胞癌(RCC)的大部分,其预后较差。本研究的目的是为ccRCC患者筛选新的预后生物标志物。

方法与结果

首先,利用基因表达综合数据库收集微阵列数据用于构建加权基因共表达网络。挑选出我们最感兴趣的与预后相关的基因模块。在关键模块中进一步选择了90个枢纽基因,其中包括促性腺激素释放激素1(GNRH1)和白三烯B4受体(LTB4R)的两个基因被筛选并验证为免疫相关的预后生物标志物。基于几个公共数据库和我们自己收集的ccRCC组织,我们进行了生存分析、斯皮尔曼相关性分析、受试者工作特征(ROC)分析、定量实时PCR(qRT-PCR)、蛋白质免疫印迹、免疫荧光(IF)和免疫组织化学(IHC)染色,以验证免疫相关的预后生物标志物。我们进一步探讨了免疫相关预后生物标志物表达与免疫细胞之间的关系。最后,基因集富集分析(GSEA)表明这两个免疫相关的预后生物标志物与细胞周期显著相关。

结论

总体而言,本研究为ccRCC患者鉴定了两个新的预后生物标志物,它们与ccRCC患者的预后密切相关,可进一步用作ccRCC潜在的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/a36f8a196ccb/12935_2021_2052_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/4d35c49d2f24/12935_2021_2052_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/7b94ba9a6726/12935_2021_2052_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/dad2c7abd5ff/12935_2021_2052_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/cb1ac6a5c208/12935_2021_2052_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/7bdba28a5416/12935_2021_2052_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/51769b03b2df/12935_2021_2052_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/89fa095c7d30/12935_2021_2052_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/978fef25d135/12935_2021_2052_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/a36f8a196ccb/12935_2021_2052_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/4d35c49d2f24/12935_2021_2052_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/7b94ba9a6726/12935_2021_2052_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/dad2c7abd5ff/12935_2021_2052_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/cb1ac6a5c208/12935_2021_2052_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/7bdba28a5416/12935_2021_2052_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/51769b03b2df/12935_2021_2052_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/89fa095c7d30/12935_2021_2052_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/978fef25d135/12935_2021_2052_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/8259034/a36f8a196ccb/12935_2021_2052_Fig9_HTML.jpg

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