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异常脑表达的X连锁4(BEX4)表达是胃癌中一种新的预后生物标志物。

Aberrant brain-expressed X-linked 4 (BEX4) expression is a novel prognostic biomarker in gastric cancer.

作者信息

Zhu Chenhong, Xiao Deshuang

机构信息

Department of General surgery, The First People's Hospital of WenLing, Wenling, Zhejiang, China.

出版信息

Medicine (Baltimore). 2020 Nov 20;99(47):e23133. doi: 10.1097/MD.0000000000023133.

DOI:10.1097/MD.0000000000023133
PMID:33217815
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7676604/
Abstract

BACKGROUND

This study aimed to investigate the expression level of X-linked 4 (BEX4) in patients with gastric cancer (GC) and to investigate the prognostic significance of BEX4.

METHODS

The mRNA expression of BEX4 was analyzed using the Cancer Genome Atlas (TCGA) datasets. The relationship between the expression of BEX4 and GC patient survival was assessed using a Kaplan-Meier plot and Log Rank test. Multivariate cox regression analysis was used to evaluate prognostic factor. The diagnostic value of BEX4 expression in GC tissue was determined through receiver operating characteristic (ROC) curve analysis. Gene set enrichment analysis (GSEA) was used to explore BEX-4 related signaling pathways in GC. Furthermore, the Human Protein Atlas (HPA) database and GSE62254 dataset were used for further validation.

RESULTS

BEX4 was expressed at lower level in GC tissues than normal gastric tissues. The lower expression of BEX4 was also validated at protein level in HPA database. The area under the ROC curve for BEX4 expression in normal gastric tissue and GC was 0.791, which presented modest diagnostic value. Kaplan-Meier survival analysis revealed that patients in low BEX4 expression group had a worse prognosis than those with high BEX4 expression (P = .009). Multivariate analysis showed that BEX4 is an independent risk factor for overall survival both in TCGA and GSE62254 (P = .0142, .013, respectively). GSEA identified that the expression of BEX4 was related to DNA replication, RNA polymerase, cell cycle, and P53 signaling pathway.

CONCLUSION

BEX4 is expressed at low levels in GC. BEX4 expression independently predicted poor OS for GC. It is a promising independent molecular predictor for the diagnosis and prognosis of GC.

摘要

背景

本研究旨在调查X连锁4(BEX4)在胃癌(GC)患者中的表达水平,并探讨BEX4的预后意义。

方法

使用癌症基因组图谱(TCGA)数据集分析BEX4的mRNA表达。使用Kaplan-Meier曲线和对数秩检验评估BEX4表达与GC患者生存率之间的关系。多变量cox回归分析用于评估预后因素。通过受试者工作特征(ROC)曲线分析确定BEX4表达在GC组织中的诊断价值。基因集富集分析(GSEA)用于探索GC中与BEX-4相关的信号通路。此外,使用人类蛋白质图谱(HPA)数据库和GSE62254数据集进行进一步验证。

结果

BEX4在GC组织中的表达水平低于正常胃组织。BEX4的低表达在HPA数据库的蛋白质水平上也得到了验证。正常胃组织和GC中BEX4表达的ROC曲线下面积为0.791,具有一定的诊断价值。Kaplan-Meier生存分析显示,BEX4低表达组患者的预后比高BEX4表达组患者差(P = 0.009)。多变量分析表明,BEX4是TCGA和GSE62254中总生存的独立危险因素(分别为P = 0.0142、0.013)。GSEA确定BEX4的表达与DNA复制、RNA聚合酶、细胞周期和P53信号通路有关。

结论

BEX4在GC中低表达。BEX4表达独立预测GC的不良总生存期。它是GC诊断和预后的一个有前景的独立分子预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8de/7676604/b976c667b4ef/medi-99-e23133-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8de/7676604/b91239c79ed1/medi-99-e23133-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8de/7676604/259b287d801f/medi-99-e23133-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8de/7676604/76f3c43a7643/medi-99-e23133-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8de/7676604/78d2da59aaad/medi-99-e23133-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8de/7676604/b976c667b4ef/medi-99-e23133-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8de/7676604/b91239c79ed1/medi-99-e23133-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8de/7676604/259b287d801f/medi-99-e23133-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8de/7676604/76f3c43a7643/medi-99-e23133-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8de/7676604/78d2da59aaad/medi-99-e23133-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8de/7676604/b976c667b4ef/medi-99-e23133-g005.jpg

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