Prognostic implications of netrin-1 expression and its receptors in patients with adenocarcinoma of the pancreas
Prognostic implications of netrin-1 expression and its receptors in patients with adenocarcinoma of the pancreas
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DOI：
10.1245/s10434-007-9469-6
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发表时间：
2007-09-01
影响因子：
3.7
通讯作者：
Yekebas, Emre F.
中科院分区：
文献类型：
--
作者：
Link, Bjoern-Christian;Reichelt, Uta;Yekebas, Emre F.
背景：探讨netrin-1及其受体在胰腺导管癌中的表达与预后的关系。方法：采用免疫组织化学方法检测82例可切除的胰腺癌组织中netrin-1、在结直肠癌中缺失的蛋白、uc5H3和新生素的表达情况。结果：中位随访期为15+/-19.9个月(范围4-108个月)。Netrin-1无表达或很少表达的患者(n=67)的中位无复发生存期为10个月(95%CI，7~13个月)，而Netrin-1中强表达的患者(n=15)的中位无复发生存期仅为4个月(95%CI，3~5个月，p=0.0165)。总生存率和无复发生存率在不同的DCC、unc5H3或negenin表达模式之间无显著差异。Netrin-1的表达对低分化肿瘤患者的总体生存有显著影响(p=0.001)。按结节状态分层分析发现，UNK5H3的表达对PN1状态患者的总体生存有显著影响(p=0.007)。结论：Netrin-1在胰腺癌中的表达对肿瘤复发时间有显著影响。Netrin-1的表达与低分化胰腺癌的不良预后有关。根据UNC5H3受体表达模式进行的风险分层显示，无或极少量表达UNC5H3的结节阳性患者(PN1)的预后明显差于那些中至强表达的患者。
Background: To assess the interaction between the expression of netrin-1 or of its receptors to the prognosis of ductal adenocarcinoma of the pancreas.Methods: In 82 patients with resectable pancreatic adenocarcinoma who underwent curative operation, the expression patterns of netrin-1, deleted in colorectal carcinomas (DCC), UNC5H3, and neogenin were determined by immunohistochemical staining. Kaplan-Meier analysis was performed to assess the prognostic relevance of the examined expression patterns.Results: Median follow-up was 15 +/- 19.9 months (range, 4-108 months). Patients suffering from tumors with no or little expression of netrin-1 (n = 67) had a median recurrence-free survival of 10 months (95% CI, 7-13 months), while a middle to strong expression (n = 15) was associated with a significantly worse median recurrence-free survival of only four months (95% CI, three to five months, p = 0.0165). Overall and recurrence-free survival showed no significant differences between the different expression patterns of DCC, UNC5H3 or neogenin. Netrin-1 expression had significant impact (p = 0.001) on overall survival of patients suffering from poorly differentiated tumors. Stratification according to the nodal status revealed significant influence (p = 0.007) of UNC5H3 expression on the overall survival of patients with pN1 status.Conclusions: Expression of netrin-1 has significant impact on time to tumor relapse in adenocarcinoma of the pancreas. Netrin-1 expression is associated with worse outcome in poorly differentiated pancreatic adenocarcinomas. Risk-stratification according to the UNC5H3 receptor expression pattern shows that node positive patients (pN1) with no to little UNC5H3 expression carry a significantly worse prognosis than those with middle to strong UNC5H3 expression.