Overexpression of GPNMB predicts an unfavorable outcome of epithelial ovarian cancer
Overexpression of GPNMB predicts an unfavorable outcome of epithelial ovarian cancer
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DOI：
10.1007/s00404-018-4699-3
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发表时间：
2018-05-01
影响因子：
2.6
通讯作者：
Cui, Heng
中科院分区：
文献类型：
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作者：
Ma, Rui-qiong;Tang, Zhi-jian;Cui, Heng
糖蛋白非转移蛋白B （GPNMB）是一种跨膜糖蛋白，在几种恶性人体组织中的表达水平高于匹配的正常组织。因此，GPNMB可能作为一个有吸引力的癌症治疗靶点。在这项研究中，GPNMB表达在一组上皮性卵巢癌（EOC）患者肿瘤中的预后价值进行了研究。通过免疫组织化学（IHC）检测匹配的福尔马林固定和石蜡包埋组织样本中GPNMB的表达，而采用实时定量PCR （qPCR）检测新鲜冷冻活检组织中GPNMB mRNA的表达。同时评估GPNMB表达与EOC临床特征的相关性。生存率数据分别采用Kaplan-Meier和Cox回归分析。与正常卵巢对照相比，GPNMB在EOC组织中的mRNA和蛋白水平均显著上调。此外，GPNMB在EOC中的高表达与FIGO分期（P < 0.001）、肿瘤残留（P = 0.036）、淋巴结转移（P = 0.004）相关。此外，单因素和多因素分析结果表明，GPNMB表达水平是影响EOC患者无进展生存期（PFS）和总生存期（OS）的独立预后因素（P < 0.001和P < 0.001）。EOC患者GPNMB水平上调与预后不良相关。此外，目前的研究结果表明，GPNMB是EOC治疗方法的潜在有用的预后预测因子。
Glycoprotein non-metastatic protein B (GPNMB) is a transmembrane glycoprotein that is expressed at higher levels in several malignant human tissues than those in matched normal tissues. Thus, GPNMB may serve as an attractive therapeutic target of cancer treatment. In this study, the prognostic value of GPNMB expression was examined in tumors derived from a cohort of patients with epithelial ovarian cancer (EOC).GPNMB expression in matched formalin-fixed and paraffin-embedded tissue samples was evaluated by immunohistochemistry (IHC), whereas GPNMB mRNA expression in fresh-frozen biopsy tissues was detected using real-time quantitative PCR (qPCR). Meanwhile, the correlations of GPNMB expression with the clinical characteristics of EOC were assessed. Besides, survival data were analysed using Kaplan-Meier and Cox regression analyses, respectively.GPNMB expression was remarkably upregulated in EOC tissues compared with that in normal ovarian controls at both mRNA and protein levels. In addition, abundant GPNMB expression in EOC was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001), residual tumor (P = 0.036), and lymph node metastasis (P = 0.004). Furthermore, results of univariate and multivariate analyses indicated that GPNMB expression level was an independent prognostic factor of the progression-free survival (PFS) and overall survival (OS) (P < 0.001 and P < 0.001, respectively) for EOC patients.Upregulated GPNMB levels in EOC patients are associated with dismal prognosis. Moreover, findings in the current study indicate that GPNMB is a potentially useful prognostic predictor of the therapeutic approaches for EOC.