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血管抑制素-2在胰腺导管腺癌中的表达促进肿瘤进展,并与不良临床预后相关。

Expression of vasohibin-2 in pancreatic ductal adenocarcinoma promotes tumor progression and is associated with a poor clinical outcome.

作者信息

Kim Jung-Chul, Kim Kyung-Tae, Park Jong-Tae, Kim Hyun-Jong, Sato Yasufumi, Kim Hyung-Seok

出版信息

Hepatogastroenterology. 2015 Mar-Apr;62(138):251-6.

PMID:25916042
Abstract

This study aimed to assess the expression of vasohibin-2 (VASH2) in pancreatic ductal adenocarcinoma (PDAC) as a marker of tumor aggressiveness and its impact on tumor angiogenesis, proliferation, and clinical outcome. We examined the expression of the VASH2 gene in human pancreatic cell lines PANC-1 and MiaPaCa-2 by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunocytochemistry. Fifty samples from patients with PDAC were immunostained with VASH2, CD34, and Ki-67 antibodies. Further, the immunoreactivity of VASH2 correlated with the pathological features, including microvessel density (MVD), tumor cell proliferation (Ki-67 labeling index), and survival. Forty-seven of the 50 samples from PDAC patients showed immunoreactivity for VASH2 along the tumor cell cytoplasm. Among the VASH2-positive samples, 22 were categorized as high VASH2 expression group, and this group had statistical significance with pN stage (p = 0.006), UICC stage (p = 0.033), tumor proliferation (p < 0.001), and MVD (p = 0.017). Moreover, patients with high VASH2 expression showed worse prognosis compared to those showing low VASH2 expression (overall logrank p = 0.003). Thus, our results suggested that overexpression of VASH2 accelerated the pace of tumor development toward a more serious malignant phenotype and was associated with a poor clinical outcome. VASH2 may be an important novel target for the management of PDAC after surgery.

摘要

本研究旨在评估血管抑制素-2(VASH2)在胰腺导管腺癌(PDAC)中的表达,将其作为肿瘤侵袭性的标志物,并研究其对肿瘤血管生成、增殖及临床结局的影响。我们通过定量逆转录聚合酶链反应(qRT-PCR)和免疫细胞化学检测了人胰腺细胞系PANC-1和MiaPaCa-2中VASH2基因的表达。用VASH2、CD34和Ki-67抗体对50例PDAC患者的样本进行免疫染色。此外,VASH2的免疫反应性与病理特征相关,包括微血管密度(MVD)、肿瘤细胞增殖(Ki-67标记指数)和生存率。50例PDAC患者样本中有47例显示肿瘤细胞胞质内VASH2呈免疫反应性。在VASH2阳性样本中,22例被归类为高VASH2表达组,该组在pN分期(p = 0.006)、UICC分期(p = 0.033)、肿瘤增殖(p < 0.001)和MVD(p = 0.017)方面具有统计学意义。此外,与低VASH2表达患者相比,高VASH2表达患者的预后更差(总体对数秩检验p = 0.003)。因此,我们的结果表明,VASH2的过表达加速了肿瘤向更严重恶性表型发展的进程,并与不良临床结局相关。VASH2可能是PDAC术后治疗的一个重要新靶点。

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