LOX-1 is a poor prognostic indicator and induces epithelial-mesenchymal transition and metastasis in pancreatic cancer patients.

LOX-1 is a poor prognostic indicator and induces epithelial-mesenchymal transition and metastasis in pancreatic cancer patients.
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LOX-1是一个不良预后指标,可诱导胰腺癌患者上皮间质转化和转移。

DOI:
10.1007/s13402-017-0360-6
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发表时间:
2018
期刊:
Cell Oncol (Dordr)
影响因子:
--
通讯作者:
Gu Jianxin
Gu Jianxin
中科院分区:
其他
文献类型:
--
作者:
Zhang Jie;Zhang Lei;Li Can;Yang Caiting;Li Lili;Song Shushu;Wu Hao;Liu Fenglin;Wang Lan;Gu Jianxin

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胰腺癌(pancreatic cancer,PC)是一种进展迅速的恶性肿瘤.以前已经发现LOX-1(其是在内皮细胞中表达的II型跨膜糖蛋白)参与几种类型的癌症的发展。然而,到目前为止,LOX-1的表达及其在PC中的功能性后果尚未被记录。本研究的目的是探讨PC患者的LOX-1表达的预后相关性,并在解决其在PC transmittance.MethodsLOX-1表达的作用进行了评估,免疫组化的组织芯片包含98例PC患者的样本。Kaplan-Meier分析比较生存曲线,考克斯回归分析探讨LOX-1表达对PC患者总生存期(OS)的独立预后价值。Harrel的一致性指数被用来计算所建立的模型的预测精度。此外,使用体外划痕伤口愈合和Transwell测定来评估LOX-1表达沉默和过表达对PC细胞迁移和侵袭的影响,采用细胞计数试剂盒(CCK-8)和流式细胞术(FCM)检测LOX-1对PC细胞增殖和凋亡的影响。LOX-1在PC肿瘤组织中高表达,与淋巴结转移、TNM分期高和OS差有关。我们还发现LOX-1表达可能作为PC患者OS的独立预后因素。我们的体外实验表明LOX-1的表达可能通过上皮间质转化(EMT)促进PC细胞的迁移和侵袭。PC细胞增殖没有影响noted.ConclusionsFrom我们的数据,我们得出结论,高LOX-1在PC组织中的表达是指淋巴结转移的发生,高TNM分期和预后不良。LOX-1可作为独立的预后生物标志物。我们的体外试验还显示LOX-1可以通过EMT增强PC细胞的迁移和侵袭。LOX-1也可以作为一个新的治疗靶点。
PurposePancreatic cancer (PC) is an aggressive type of cancer that exhibits a rapid progression. Previously LOX-1, which is a type II trans-membrane glycoprotein that is expressed in endothelial cells, has been found to be involved in the development of several types of cancer. As yet, however, the expression of LOX-1 and its functional consequences in PC have not been documented. The present study was aimed at investigating the prognostic relevance of LOX-1 expression in PC patients and at resolving its role in PC metastasis.MethodsLOX-1 expression was assessed by immunohistochemistry on a tissue microarray containing samples from 98 PC patients. Kaplan-Meier analyses were performed to compare survival curves, whereas Cox regression analyses were performed to explore the independent prognostic value of LOX-1 expression on the overall survival (OS) of PC patients. Harrel’s concordance index was applied to calculate the predictive accuracy of established models. In addition, in vitro scratch wound healing and Transwell assays were used to assess the effect of LOX-1 expression silencing and over-expression on PC cell migration and invasion, whereas Cell Counting Kit-8 (CCK8) and Flow Cytometry (FCM) assays were used to assess its effects on PC cell proliferation and apoptosis.ResultsWe found that LOX-1 is highly expressed in the PC tumor tissues tested and is related to the occurrence of lymph node metastases, higher TNM stages and a poor OS. We also found that LOX-1 expression may serve as an independent prognostic factor for the OS of PC patients. Our in vitro assays revealed that LOX-1 expression may promote the migration and invasion of PC cells through epithelial-mesenchymal transition (EMT). No effect on PC cell proliferation was noted.ConclusionsFrom our data we conclude that a high LOX-1 expression in PC tissues is indicative for the occurrence of lymph node metastases, high TNM stages and a poor prognosis. LOX-1 may serve as an independent prognostic biomarker. Our in vitro assays additionally revealed that LOX-1 may enhance the migration and invasion of PC cells through EMT. LOX-1 may also serve as a novel therapeutic target.