氨肽酶N/CD13在人胰腺癌中的表达的临床意义
Clinical significance of aminopeptidase N/CD13 expression in human pancreatic carcinoma.
作者信息
Ikeda Naoya, Nakajima Yoshiyuki, Tokuhara Takahiro, Hattori Noboru, Sho Masayuki, Kanehiro Hiromichi, Miyake Masayuki
机构信息
The Fifth Department of Oncology and the Department of Thoracic Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka 530-8480, Japan.
出版信息
Clin Cancer Res. 2003 Apr;9(4):1503-8.
PURPOSE
We previously established a novel murine monoclonal antibody(MH8-11) that recognized aminopeptidase N (APN)/cluster of differentiation antigen 13 (CD13). This monoclonal antibody inhibited human umbilical vein endothelial cells migration and capillary-like tube formation of human umbilical vein endothelial cells on Matrigel. In this study, we investigated the expression of APN/CD13 and the intratumor microvessel density (IMD) as the number of microvessel counts in 50 patients with pancreatic carcinoma.
EXPERIMENTAL DESIGN
We investigated APN/CD13 gene expression using the reverse transcriptase-PCR. We also used immunohistochemistry with MH8-11 to investigate APN/CD13 protein expression. Moreover, we investigated the relationship between APN/CD13 expression and tumor angiogenesis by measuring the IMD.
RESULTS
APN/CD13 gene expression detected by reverse transcriptase-PCR was positive in 50.0% (25 of 50) of the tumors, and APN/CD13 protein positive was detected by immunohistochemistry in 48.0% (24 of 50). APN/CD13 gene expression agreed well with the immunohistochemical findings (90.0% concordance). APN/CD13 was also significantly associated with an increase of the IMD (r = 0.71, P = 0.0003). However, APN/CD13 expression was not associated with various prognostic factors. The median survival time of patients with APN/CD13 expression was significantly shorter than that of patients without APN/CD13 expression (P = 0.009), and multivariate analysis showed that the APN/CD13 status was a significant independent factor (P = 0.016).
CONCLUSIONS
Our data suggest that APN/CD13 may be a new prognostic marker for patients with pancreatic carcinoma and may have a relationship with the angiogenesis for this cancer.
目的
我们先前制备了一种新型鼠单克隆抗体(MH8-11),它可识别氨肽酶N(APN)/分化抗原簇13(CD13)。该单克隆抗体可抑制人脐静脉内皮细胞迁移以及人脐静脉内皮细胞在基质胶上形成毛细血管样管腔。在本研究中,我们调查了50例胰腺癌患者中APN/CD13的表达情况以及作为微血管计数的肿瘤内微血管密度(IMD)。
实验设计
我们使用逆转录聚合酶链反应(RT-PCR)研究APN/CD13基因表达。我们还使用MH8-11进行免疫组织化学以研究APN/CD13蛋白表达。此外,我们通过测量IMD来研究APN/CD13表达与肿瘤血管生成之间的关系。
结果
通过RT-PCR检测,50.0%(50例中的25例)的肿瘤中APN/CD13基因表达呈阳性,通过免疫组织化学检测,48.0%(50例中的24例)的肿瘤中APN/CD13蛋白呈阳性。APN/CD13基因表达与免疫组织化学结果高度一致(一致性为90.0%)。APN/CD13也与IMD的增加显著相关(r = 0.71,P = 0.0003)。然而,APN/CD13表达与各种预后因素无关。APN/CD13表达阳性患者的中位生存时间显著短于APN/CD13表达阴性患者(P = 0.009),多因素分析显示APN/CD13状态是一个显著的独立因素(P = 0.016)。
结论
我们的数据表明,APN/CD13可能是胰腺癌患者的一种新的预后标志物,并且可能与该癌症的血管生成有关。