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IMP3作为预测胃肠胰神经内分泌肿瘤预后不良标志物的表达

Expression of IMP3 as a marker for predicting poor outcome in gastroenteropancreatic neuroendocrine neoplasms.

作者信息

Er Li-Mian, Li Yong, Wu Ming-Li, Zhao Qun, Tan Bi-Bo, Wang Xiao-Ling, Wang Shi-Jie

机构信息

Department of Endoscopy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

出版信息

Oncol Lett. 2017 Apr;13(4):2391-2396. doi: 10.3892/ol.2017.5735. Epub 2017 Feb 14.

Abstract

The aim of the present study was to investigate the expression and clinical significance of oncofetal protein insulin-like growth factor (IGF) II mRNA-binding protein 3 (IMP3) in the differentiation of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). A total of 162 patients who were diagnosed with GEP-NEN, and who underwent surgical or endoscopic resection from January 2006 to March 2013, were enrolled in the study, including 85 cases of grade (G)1 neuroendocrine tumors, 40 cases of G2 neuroendocrine tumors, 28 cases of G3 neuroendocrine carcinomas and 9 cases of mixed stage adenoneuroendocrine carcinomas. The clinical and pathological data were recorded for analysis. The expression of IMP3, cluster of differentiation (CD)44, IGF1 receptor (IGF1R) and matrix metalloproteinase (MMP)2 was determined by immunohistochemistry. SPSS 13.0 software was used for data processing and analyses, and P<0.05 was used to determine significance. Oncofetal protein IMP3 exhibited a high expression rate (74.69%) in GEP-NEN. IMP3-positive cases demonstrated significantly decreased overall and disease-free survival times, as compared with IMP3-negative cases (P=0.012). Overexpression of IMP3 was correlated with tumor grade, clinical stage, tumor size and poor prognosis (all P<0.05). Therefore, patients with overexpressed IMP3 had a poorer prognosis (P<0.01); COX regression analysis revealed that the overexpression of IMP3, the tumor grade, tumor size and metastasis of GEP-NEN were each associated with the clinical outcomes. The results also indicated that the expression rates of CD44, IGF1R and MMP2 in GEP-NEN were 19.75, 53.7 and 55.56%, respectively. While it was negatively associated with the expression of CD44 (r=-0.131; P=0.096), the expression of IMP3 was positively correlated with the expression of IGF1R and MMP2 (r=0.288, P<0.01; r=0.208, P=0.008). In addition, the expression levels of IGF1R and MMP2 were positively associated (r=0.687; P<0.01). In conclusion, high IMP3 expression levels were determined to be associated with a high disease stage in patients with GEP-NEN, thus it may serve as a predictor for metastasis and poor clinical outcomes in GEP-NEN.

摘要

本研究旨在探讨癌胚蛋白胰岛素样生长因子(IGF)II mRNA结合蛋白3(IMP3)在胃肠胰神经内分泌肿瘤(GEP-NEN)分化中的表达及临床意义。纳入2006年1月至2013年3月期间诊断为GEP-NEN并接受手术或内镜切除的162例患者,其中包括85例1级(G)神经内分泌肿瘤、40例G2神经内分泌肿瘤、28例G3神经内分泌癌和9例混合期腺神经内分泌癌。记录临床和病理数据进行分析。采用免疫组织化学法检测IMP3、分化簇(CD)44、IGF1受体(IGF1R)和基质金属蛋白酶(MMP)2的表达。使用SPSS 13.0软件进行数据处理和分析,以P<0.05为差异有统计学意义。癌胚蛋白IMP3在GEP-NEN中呈现高表达率(74.69%)。与IMP3阴性病例相比,IMP3阳性病例的总生存期和无病生存期显著缩短(P=0.012)。IMP3的过表达与肿瘤分级、临床分期、肿瘤大小及预后不良相关(均P<0.05)。因此,IMP3过表达的患者预后较差(P<0.01);COX回归分析显示,IMP3的过表达、GEP-NEN的肿瘤分级、肿瘤大小及转移均与临床结局相关。结果还表明,GEP-NEN中CD44、IGF1R和MMP2的表达率分别为19.75%、53.7%和55.56%。IMP3的表达与CD44的表达呈负相关(r=-0.131;P=0.096),而与IGF1R和MMP2的表达呈正相关(r=0.288,P<0.01;r=0.208,P=0.008)。此外,IGF1R和MMP2的表达水平呈正相关(r=0.687;P<0.01)。总之,确定IMP3高表达水平与GEP-NEN患者的高疾病分期相关,因此它可能作为GEP-NEN转移和不良临床结局的预测指标。

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