氯离子细胞内通道（CLIC）相互作用组的转录组分析确定了胰腺导管腺癌患者中七个预后标志物的分子组。
Transcriptomic Analysis of the Chloride Intracellular Channels (CLIC) Interactome Identifies a Molecular Panel of Seven Prognostic Markers in Patients with Pancreatic Ductal Adenocarcinoma.
作者信息
Magouliotis Dimitrios E, Sakellaridis Nikos, Dimas Konstantinos, Tasiopoulou Vasiliki S, Svokos Konstantina A, Svokos Alexis A, Zacharoulis Dimitris
机构信息
1Division of Surgery and Interventional Science, Faculty of Medical Sciences, UCL, London, UK and Department of Surgery, University of Thessaly, Biopolis, Larissa, Greece; 2Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece; 3Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece; 4Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece; 5The Warren Alpert Medical School of Brown University, Providence, RI, USA; 6Geisinger Medical Center, Danville, PA, USA; 7Department of Surgery, University Hospital of Larissa, Larissa, Greece.
出版信息
Curr Genomics. 2020 Feb;21(2):119-127. doi: 10.2174/1389202921666200316115631.
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. In this context, the identification of biomarkers regarding the PDAC diagnosis, monitoring, and prognosis is crucial.
OBJECTIVES
The purpose of the current study was to investigate the differential gene expression profile of the chloride intracellular channel (CLIC) gene family network in patients with PDAC, in order to suggest novel biomarkers.
METHODS
techniques were used to construct the interactome of the CLIC gene family, identify the differentially expressed genes (DEGs) in PDAC as compared to healthy controls, and evaluate their potential prognostic role.
RESULTS
Transcriptomic data of three microarray datasets were included, incorporating 114 tumor and 59 normal pancreatic samples. Twenty DEGs were identified; eight were up-regulated and twelve were downregulated. A molecular signature of seven genes (Chloride Intracellular Channel 1 - CLIC1; Chloride Intracellular Channel 3 - CLIC3; Chloride Intracellular Channel 4 - CLIC4; Ganglioside Induced Differentiation Associated Protein 1 - GDAP1; Ganglioside Induced Differentiation Associated Protein 1 Like 1 - GDAP1L1; Glutathione S-Transferase Pi 1 - GSTP1; Prostaglandin E Synthase 2 - PTGES2) were identified as prognostic markers associated with overall survival. Positive correlations were reported regarding the expression of CLIC1-CLIC3, CLIC4-CLIC5, and CLIC5-CLIC6. Finally, gene set enrichment analysis demonstrated the molecular functions and miRNA families (hsa-miR-122, hsa-miR-618, hsa-miR-425, and hsa-miR-518) relevant to the seven prognostic markers.
CONCLUSION
These outcomes demonstrate a seven-gene molecular panel that predicts the patients' prospective survival following pancreatic resection for PDAC.
背景
胰腺导管腺癌（PDAC）预后较差。在此背景下，识别与PDAC诊断、监测及预后相关的生物标志物至关重要。
目的
本研究旨在探究PDAC患者中氯离子细胞内通道（CLIC）基因家族网络的差异基因表达谱，以提出新的生物标志物。
方法
运用相关技术构建CLIC基因家族的相互作用组，识别与健康对照相比PDAC中差异表达基因（DEGs），并评估其潜在预后作用。
结果
纳入三个微阵列数据集的转录组数据，包括114个肿瘤胰腺样本和59个正常胰腺样本。识别出20个DEGs；8个上调，12个下调。确定了一个由七个基因组成的分子特征（氯离子细胞内通道1 - CLIC1；氯离子细胞内通道3 - CLIC3；氯离子细胞内通道4 - CLIC4；神经节苷脂诱导分化相关蛋白1 - GDAP1；神经节苷脂诱导分化相关蛋白1样蛋白1 - GDAP1L1；谷胱甘肽S-转移酶Pi 1 - GSTP1；前列腺素E合酶2 - PTGES2）作为与总生存期相关的预后标志物。报告了CLIC1-CLIC3、CLIC4-CLIC5和CLIC5-CLIC6表达之间的正相关。最后，基因集富集分析证明了与这七个预后标志物相关的分子功能和miRNA家族（hsa-miR-122、hsa-miR-618、hsa-miR-425和hsa-miR-518）。
结论
这些结果证明了一个七基因分子组可预测PDAC胰腺切除术后患者的预期生存期。
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