DEK Is a Potential Biomarker Associated with Malignant Phenotype in Gastric Cancer Tissues and Plasma
DEK Is a Potential Biomarker Associated with Malignant Phenotype in Gastric Cancer Tissues and Plasma
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DOI：
10.3390/ijms20225689
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Lin, Kwang-Huei
中科院分区：
文献类型：
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作者：
Lee, Kam-Fai;Tsai, Ming-Ming;Lin, Kwang-Huei
胃癌（GC）是全球癌症相关死亡的第二大常见原因。新型癌蛋白生物标志物的发现可促进胃癌治疗策略的发展。在本研究中，我们通过整合相对和绝对定量同位素标记（iTRAQ）、人类血浆蛋白质组数据库以及公共的Oncomine数据集来鉴定新型生物标志物，以寻找胃癌组织和血浆中异常表达的癌基因相关蛋白。选择了其中上调最显著的生物标志物之一DEK，并对其表达进行了验证。我们的免疫组化（IHC）（n = 92）和实时定量聚合酶链反应（qRT - PCR）（n = 72）分析显示，与配对的非肿瘤黏膜相比，肿瘤组织中DEK的表达显著增加。重要的是，通过酶联免疫吸附测定（ELISA）检测到胃癌患者术前血浆DEK水平明显高于健康对照组。在临床病理分析中，组织和血浆中DEK的高表达与胃癌患者的晚期阶段和较差的生存结果显著相关。接受者操作特征（ROC）曲线分析的数据显示，血浆DEK比癌胚抗原（CEA）、糖类抗原19.9（CA 19.9）和C - 反应蛋白（CRP）具有更好的诊断准确性，突显了其作为胃癌有效血浆生物标志物的潜力。血浆DEK在肿瘤检测中也比其他三种生物标志物更敏感。DEK的敲低通过一种涉及调节基质金属蛋白酶MMP - 2/MMP - 9水平的机制导致胃癌细胞迁移受到抑制，反之亦然。我们的研究结果共同支持血浆DEK作为胃癌患者诊断和预后的有用生物标志物。
Gastric cancer (GC) is the second most widespread cause of cancer-related mortality worldwide. The discovery of novel biomarkers of oncoproteins can facilitate the development of therapeutic strategies for GC treatment. In this study, we identified novel biomarkers by integrating isobaric tags for relative and absolute quantitation (iTRAQ), a human plasma proteome database, and public Oncomine datasets to search for aberrantly expressed oncogene-associated proteins in GC tissues and plasma. One of the most significantly upregulated biomarkers, DEK, was selected and its expression validated. Our immunohistochemistry (IHC) (n = 92) and quantitative real-time polymerase chain reaction (qRT-PCR) (n = 72) analyses disclosed a marked increase in DEK expression in tumor tissue, compared with paired nontumor mucosa. Importantly, significantly higher preoperative plasma DEK levels were detected in GC patients than in healthy controls via enzyme-linked immunosorbent assay (ELISA). In clinicopathological analysis, higher expression of DEK in both tissue and plasma was significantly associated with advanced stage and poorer survival outcomes of GC patients. Data from receiver operating characteristic (ROC) curve analysis disclosed a better diagnostic accuracy of plasma DEK than carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA 19.9), and C-reactive protein (CRP), highlighting its potential as an effective plasma biomarker for GC. Plasma DEK is also more sensitive in tumor detection than the other three biomarkers. Knockdown of DEK resulted in inhibition of GC cell migration via a mechanism involving modulation of matrix metalloproteinase MMP-2/MMP-9 level and vice versa. Our results collectively support plasma DEK as a useful biomarker for making diagnosis and prognosis of GC patients.