Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Sci Rep. 2018 Jun 29;8(1):9846. doi: 10.1038/s41598-018-28253-9.
Lysyl oxidase (LOX) family genes, particularly lysyl oxidase-like protein 2 (LOXL2), have been implicated in carcinogenesis, metastasis, and the epithelial-to-mesenchymal transition (EMT) in various cancers. This study aimed to explore the clinical implications of LOXL2 expression in pancreatic cancer (PC) in the context of EMT status. LOX family mRNA expression was measured in PC cell lines, and LOXL2 protein levels were examined in surgical specimens resected from 170 patients with PC. Higher LOXL2 expression was observed in cell lines from mesenchymal type PC than in those from epithelial type PC. A significant correlation between LOXL2 expression and the EMT status defined based on the expression of E-cadherin and vimentin was observed in surgical specimens (P < 0.01). The disease-free survival and overall survival rates among patients with low LOXL2 expression were significantly better than those among patients with high LOXL2 expression (P < 0.001). According to the multivariate analysis, high LOXL2 expression (P = 0.03) was a significant independent prognostic factor for patients with PC. Additionally, LOX inhibition significantly decreased PC cell proliferation, migration, and invasion in vitro. In conclusion, LOXL2 expression is potentially associated with PC progression, and LOXL2 expression represents a biomarker for predicting the prognosis of patients with PC who have undergone complete resection.
赖氨酰氧化酶(LOX)家族基因,尤其是赖氨酰氧化酶样蛋白 2(LOXL2),与多种癌症的发生、转移和上皮间质转化(EMT)有关。本研究旨在探讨 EMT 状态背景下 LOXL2 表达在胰腺癌(PC)中的临床意义。测量了 PC 细胞系中的 LOX 家族 mRNA 表达,并检查了 170 例 PC 手术标本中的 LOXL2 蛋白水平。在间质型 PC 细胞系中观察到 LOXL2 表达高于上皮型 PC 细胞系。在手术标本中观察到 LOXL2 表达与基于 E-钙粘蛋白和波形蛋白表达定义的 EMT 状态之间存在显著相关性(P<0.01)。低 LOXL2 表达组患者的无病生存率和总生存率明显优于高 LOXL2 表达组(P<0.001)。根据多变量分析,高 LOXL2 表达(P=0.03)是 PC 患者的一个显著独立预后因素。此外,LOX 抑制在体外显著降低了 PC 细胞的增殖、迁移和侵袭。总之,LOXL2 表达可能与 PC 的进展有关,LOXL2 表达代表了预测完全切除后 PC 患者预后的生物标志物。