Decreased LIPF expression is correlated with DGKA and predicts poor outcome of gastric cancer.
Decreased LIPF expression is correlated with DGKA and predicts poor outcome of gastric cancer.
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DOI：
10.3892/or.2016.4989
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发表时间：
2016-10
期刊：
影响因子：
4.2
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Kong Y;Zheng Y;Jia Y;Li P;Wang Y
胃癌(GC)是世界范围内常见的致命性消化道肿瘤。不幸的是，由于不典型的症状或不完全的主诉，GC的诊断通常是混淆和误导的。因此，探索基因表达谱，识别具有相似变异趋势的基因，将为胃癌的诊断和治疗带来新的视角。在这篇论文中，我们分析了高加索人胃癌及其匹配的非癌组织的RNA-Seq数据集[基因表达总表：SRP049809]，以及由肿瘤和非肿瘤组织组成的四个微阵列(GEO：GSE13911、GSE19826、GSE29272、GSE33335)的数据集，以探索差异表达基因(DGE)。结果，我们确定了373个DGE的核心集合。在这些基因中，我们发现大多数下调的基因与脂代谢功能有关。尤其是与各种脂代谢过程有关的胃脂酶(LIPF)基因在所有数据集中均显著降低。然后，我们利用胃组织阵列进行免疫组织化学实验，以研究LIPF的临床效果，以及LIPF靶基因二酰甘油激酶α(DGKA)的表达。90例胃腺癌组织中LIPF和DGKA水平均低于正常组织[LIPF为59.1%(53/90)；DGKA为77.8%(70/90)]，而正常组织为94.4%(85/90)；这两种蛋白在胃癌中的表达水平与局部侵袭和疾病分期有关。COX回归分析显示，DGKA高表达(HR，0.49；95%CI，0.26~0.94；P=0.03)预示预后良好，而淋巴结转移状态(HR，4.63；95%CI，1.39~15.51；P=0.01)预示预后不良。因此，我们推测LIPF-DGKA可能是一种潜在的诊断胃癌的生物标志物，它们的下调可能为胃癌预后的研究带来新的视角。
Gastric cancer (GC) is a common and deadly digestive tract tumor worldwide. Unfortunately, diagnosis of GC is usually confused and misleading because of atypical symptoms or incomplete complaints. Accordingly, exploring gene expression profile and identifying genes with analogical variance trend will bring new perspective into the diagnosis and treatment of GC. Herein, a RNA-Seq dataset from Caucasian GC and their matched non-cancerous samples [Gene Expression Omnibus (GEO): SRP049809] and datasets from four microarrays constituted with tumor and non-tumor tissues (GEO: GSE13911, GSE19826, GSE29272, GSE33335) were analyzed to explore the differentially expressed genes (DGEs). As a result, we identified a core set of 373 DGEs. Among these genes, we found that most downregulated genes were related to lipid-metabolic functions. Especially, the gastric lipase (LIPF) gene, which was connected with various lipid metabolism processes, was significantly decreased among all datasets. We then performed immunohistochemistry experiments using gastric tissue arrays to investigate the clinical effects, and the expression of a LIPF target gene, diacylglycerol kinase α (DGKA). Among the 90 samples of gastric adenocarcinoma, the LIPF and DGKA levels were both decreased in cancer tissues [LIPF, 59.1% (53/90); DGKA, 77.8% (70/90)] compared to normal tissues [LIPF, 94.4% (85/90); DGKA, 90% (81/90)]. The expression level of these two proteins in GC was associated with local invasion and disease stage. Cox regression identified high DGKA expression (HR, 0.49; 95% CI, 0.26–0.94; P=0.03) as a predictor of good prognosis and LNM status (HR, 4.63; 95% CI, 1.39–15.51; P=0.01) as a predictor of poor prognosis. Thus we speculated that LIPF-DGKA might serve as a potential possible biomarkers for diagnosis of GC, and their downregulation may bring new perspective into the investigation of GC prognosis.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
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通讯作者：
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