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NEDD9、E-钙黏蛋白和γ-连环蛋白在胰腺导管腺癌(PDAC)中的免疫组织化学表达及其预后意义。

Immunohistochemical expression of NEDD9, E-cadherin and γ-catenin and their prognostic significance in pancreatic ductal adenocarcinoma (PDAC).

机构信息

Department of Pathology and Cytology, Sestre Milosrdnice University Hospital, Zagreb, Croatia.

出版信息

Bosn J Basic Med Sci. 2018 Aug 1;18(3):246-251. doi: 10.17305/bjbms.2018.2378.

Abstract

Extensive research is being conducted to identify novel diagnostic, predictive and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC), as only a few markers have been routinely used so far with limited success. Our aim was to assess the expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), E-cadherin, and γ-catenin in PDAC in relation to clinicopathological parameters and patient survival. We also investigated if there is a correlation of NEDD9 expression with E-cadherin or γ-catenin. The protein expression was determined by immunohistochemistry in 61 PDAC and 61 samples of normal pancreatic tissue. The log rank test and Kaplan-Meier survival curve were used for survival analysis. E-cadherin and γ-catenin expressions were reduced in PDAC, and completely retained in normal pancreatic tissue. Expression of NEDD9 was significantly increased in PDAC (strong expression in 78.7% of cases and moderate in 21.3%) and reduced in normal pancreatic tissue (strong positivity in 45.9% of cases, moderate in 31.1%, and weak in 23%). There was a positive correlation between reduced E-cadherin and γ-catenin expression in PDAC (p = 0.015). The loss or reduced expression of E-cadherin had a negative impact on patient survival (p = 0.020). A negative correlation between E-cadherin expression and tumor grade was also observed (p = 0.011). Decreased E-cadherin expression was more common in male patients with PDAC (81.3% vs. 60% for females, p = 0.005). γ-catenin and NEDD9 expressions were not statistically correlated with tumor stage and grade, gender, nor with patient survival. Our results support the role of NEDD9, E-cadherin and γ-catenin proteins in PDAC, but further research should clarify in detail their mechanism of action in pancreatic cancer.

摘要

目前,只有少数几种标志物被常规用于胰腺导管腺癌(PDAC),且效果有限,因此,人们正在广泛研究以寻找新的诊断、预测和预后生物标志物。我们的目的是评估神经前体细胞表达的发育下调蛋白 9(NEDD9)、E-钙黏蛋白和γ-连环蛋白在 PDAC 中的表达与临床病理参数和患者生存的关系。我们还研究了 NEDD9 表达与 E-钙黏蛋白或γ-连环蛋白是否存在相关性。通过免疫组织化学法在 61 例 PDAC 和 61 例正常胰腺组织中检测到蛋白表达。对数秩检验和 Kaplan-Meier 生存曲线用于生存分析。E-钙黏蛋白和γ-连环蛋白在 PDAC 中表达减少,在正常胰腺组织中完全保留。NEDD9 的表达在 PDAC 中显著增加(78.7%的病例为强阳性,21.3%的病例为中度阳性),在正常胰腺组织中减少(45.9%的病例为强阳性,31.1%的病例为中度阳性,23%的病例为弱阳性)。PDAC 中 E-钙黏蛋白和γ-连环蛋白表达减少呈正相关(p=0.015)。E-钙黏蛋白和γ-连环蛋白表达缺失或减少对患者生存有负面影响(p=0.020)。E-钙黏蛋白表达与肿瘤分级之间也存在负相关(p=0.011)。在 PDAC 男性患者中,E-钙黏蛋白表达减少更为常见(81.3% vs. 60%,女性,p=0.005)。γ-连环蛋白和 NEDD9 的表达与肿瘤分期和分级、性别以及患者生存均无统计学相关性。我们的结果支持 NEDD9、E-钙黏蛋白和γ-连环蛋白在 PDAC 中的作用,但进一步的研究应该详细阐明它们在胰腺癌中的作用机制。

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