Integrated expression profiles analysis reveals novel predictive biomarker in pancreatic ductal adenocarcinoma.

Integrated expression profiles analysis reveals novel predictive biomarker in pancreatic ductal adenocarcinoma.
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DOI:
10.18632/oncotarget.16732
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发表时间:
2017-08-08
期刊:
影响因子:
--
通讯作者:
Shen B
Shen B
中科院分区:
其他
文献类型:
--
作者:
Li H;Wang X;Fang Y;Huo Z;Lu X;Zhan X;Deng X;Peng C;Shen B

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胰腺导管腺癌(PDAC)是人类最致命的恶性肿瘤,其5年生存率低于5%。胰腺导管腺癌早期缺乏特异性症状和生物标志物的缺乏导致诊断不佳。为了改善预后,迫切需要一种用于胰腺癌早期诊断的筛选生物标志物。我们在GEO上检索了基因表达谱数据库,旨在比较胰腺肿瘤和癌旁组织配对的基因表达谱,筛选出4个合适的基因表达谱数据系列(“GSE 15471”、“GSE 18670”、“GSE 28735”和“GSE 58561”)。经过仔细分析,13个DEG(MYOF,SLC 6A 6,S100 P,HK 2,IFI 44 L,OSBPL 3,IGF 2BP 3,PDK 4,IL 1 R2,ERO 1A,EGLN 3,PLAC 8和ACSL 5)在4个共有的微阵列数据库中显著差异表达。通过分析TCGA数据库中的mRNA表达数据和临床随访调查以及137例胰腺导管腺癌患者的临床病理资料,我们仔细地证明了这些差异表达基因中的3个(ERO 1A、OSBPL 3和IFI 44 L)与胰腺导管腺癌患者的不良预后相关。此外,我们还发现细胞-基质粘附和细胞外基质是胰腺导管腺癌中最重要的调控途径,并根据上述4个基因表达芯片数据描绘了细胞外基质相关基因的两个蛋白-蛋白相互作用网络(“GSE 15471”、“GSE 18670”、“GSE 28735”和“GSE 58561”),希望在本研究中阐明PDAC的病因学和PDAC中的耐药性机制。
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal human malignant tumor, with a dismal 5-year survival rate of less than 5%. The lack of specific symptoms at early tumor stages and the paucity of biomarkers contribute to the poor diagnosis of pancreatic ductal adenocarcinoma. To improve prognosis, a screening biomarker for early diagnosis of pancreatic cancer is in urgent need. We searched the databases of expression profiling by array on GEO, aiming at comparing gene expression profile of matched pairs of pancreatic tumor and adjacent non-tumor tissues, and we screen out 4 suitable series of gene expression microarray data (“GSE15471”, “GSE18670”, “GSE28735” and “GSE58561”). After carefully analyzing, 13 DEGs (MYOF, SLC6A6, S100P, HK2, IFI44L, OSBPL3, IGF2BP3, PDK4, IL1R2, ERO1A, EGLN3, PLAC8 and ACSL5) are significantly differentially expressed in four microarray databases in common. After analyzing mRNA expression data and clinical follow-up survey provided in the TCGA database and clinicopathological data of 137 pancreatic ductal adenocarcinoma patients, we carefully demonstrated that three of these differentially expressed genes (ERO1A, OSBPL3 and IFI44L) are correlated with poor prognosis of pancreatic ductal adenocarcinoma patients. In addition, we revealed that cell–matrix adhesion and extracellular matrix were top significantly regulated pathways in pancreatic ductal adenocarcinoma and depicted two protein-protein interactions networks of extracellular matrix related Genes which are dysregulated according to 4 gene expression microarray data mentioned above (“GSE15471”, “GSE18670”, “GSE28735” and “GSE58561”), hoping to shed light on the etiology of PDAC and mechanisms of drug resistance in PDAC in this study.
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