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全基因组分析确定GJB2和ERO1LB为胰腺癌患者的预后标志物。

Genome-scale analysis identifies GJB2 and ERO1LB as prognosis markers in patients with pancreatic cancer.

作者信息

Zhu Tao, Gao Yuan-Feng, Chen Yi-Xin, Wang Zhi-Bin, Yin Ji-Ye, Mao Xiao-Yuan, Li Xi, Zhang Wei, Zhou Hong-Hao, Liu Zhao-Qian

机构信息

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.

Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China.

出版信息

Oncotarget. 2017 Mar 28;8(13):21281-21289. doi: 10.18632/oncotarget.15068.

Abstract

Pancreatic cancer is a complex and heterogeneous disease with the etiology largely unknown. The deadly nature of pancreatic cancer, with an extremely low 5-year survival rate, renders urgent a better understanding of the molecular events underlying it. The aim of this study is to investigate the gene expression module of pancreatic adenocarcinoma and to identify differentially expressed genes (DEGs) with prognostic potentials. Transcriptome microarray data of five GEO datasets (GSE15471, GSE16515, GSE18670, GSE32676, GSE71989), including 117 primary tumor samples and 73 normal pancreatic tissue samples, were utilized to identify DEGs. The five sets of DEGs had an overlapping subset consisting of 98 genes (90 up-regulated and 8 down-regulated), which were probably common to pancreatic cancer. Gene ontology (GO) analysis of the 98 DEGs showed that cell cycle and cell adhesion were the major enriched processes, and extracellular matrix (ECM)-receptor interaction and p53 signaling pathway were the most enriched pathways according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Elevated expression of gap junction protein beta 2 (GJB2) and reduced endoplasmic reticulum oxidoreductase 1-like beta (ERO1LB) expression were validated in an independent cohort. Kaplan-Meier survival analysis revealed that GJB2 and ERO1LB levels were significantly associated with the overall survival of pancreatic cancer patients. GJB2 and ERO1LB are implicated in pancreatic cancer progression and can be used to predict patient survival. Therapeutic strategies targeting GJB2 and facilitating ERO1LB expression may deserve evaluation to improve prognosis of pancreatic cancer patients.

摘要

胰腺癌是一种复杂的异质性疾病,其病因大多未知。胰腺癌的致命性使其5年生存率极低,因此迫切需要更好地了解其潜在的分子事件。本研究的目的是调查胰腺腺癌的基因表达模块,并识别具有预后潜力的差异表达基因(DEG)。利用五个GEO数据集(GSE15471、GSE16515、GSE18670、GSE32676、GSE71989)的转录组微阵列数据,包括117个原发性肿瘤样本和73个正常胰腺组织样本,来识别DEG。这五组DEG有一个由98个基因组成的重叠子集(90个上调和8个下调),这些基因可能是胰腺癌共有的。对这98个DEG的基因本体(GO)分析表明,细胞周期和细胞黏附是主要富集的过程,根据京都基因与基因组百科全书(KEGG)通路分析,细胞外基质(ECM)-受体相互作用和p53信号通路是最富集的通路。在一个独立队列中验证了间隙连接蛋白β2(GJB2)表达升高和内质网氧化还原酶1样β(ERO1LB)表达降低。Kaplan-Meier生存分析显示,GJB2和ERO1LB水平与胰腺癌患者的总生存期显著相关。GJB2和ERO1LB与胰腺癌进展有关,可用于预测患者生存。针对GJB2并促进ERO1LB表达的治疗策略可能值得评估,以改善胰腺癌患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4ce/5400583/5a0b589735fe/oncotarget-08-21281-g001.jpg

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