Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
Oncol Rep. 2018 Jun;39(6):2664-2672. doi: 10.3892/or.2018.6349. Epub 2018 Apr 2.
In the present study, we investigated the role of lysyl oxidase‑like 2 (LOXL2), the correlation between LOXL2 and epithelial to mesenchymal transition (EMT) and the effects of using β‑aminopropionitrile (BAPN) to inhibit LOXL2 with the aim of reducing tumor progression in hepatocellular carcinoma (HCC). The expression level of LOXL2 was evaluated in HCC and adjacent non‑cancerous tissues using quantitative reverse transcription polymerase chain reaction and clinicopathological analyses. The effects of BAPN on cell proliferation, migration and invasion were investigated in vitro. Additionally, LOXL2 expression was assessed in the culture supernatants of HCC cell lines. Our results revealed that LOXL2 expression was higher in HCC cell lines and tissues. There was a significant correlation between EMT status and LOXL2 levels (P=0.004). BAPN reduced migration and invasion in HCC cells. HCC patients with high levels of LOXL2 expression had relatively shorter disease‑free survival (P=0.009) and overall survival (P=0.035). The expression level of LOXL2 was similar between cell supernatants and HCC cell lines. A multivariate analysis demonstrated that portal vein invasion (P=0.015), venous invasion (P=0.026), serum AFP (α‑fetoprotein) levels (P=0.019) and LOXL2 expression (P=0.009) were independent prognostic factors. Our results indicated that a higher level of LOXL2 may contribute to tumor progression, indicating that LOXL2 has clinical value as a therapeutic target in HCC.
在本研究中,我们研究了赖氨酰氧化酶样 2(LOXL2)的作用、LOXL2 与上皮间质转化(EMT)的相关性,以及使用β-氨基丙腈(BAPN)抑制 LOXL2 以减少肝癌(HCC)肿瘤进展的效果。使用定量逆转录聚合酶链反应和临床病理分析评估 LOXL2 在 HCC 和相邻非癌组织中的表达水平。在体外研究了 BAPN 对细胞增殖、迁移和侵袭的影响。此外,评估了 LOXL2 在 HCC 细胞系培养上清液中的表达。结果显示,LOXL2 在 HCC 细胞系和组织中的表达水平较高。EMT 状态与 LOXL2 水平之间存在显著相关性(P=0.004)。BAPN 降低了 HCC 细胞的迁移和侵袭。LOXL2 高表达的 HCC 患者无疾病生存率(P=0.009)和总生存率(P=0.035)相对较短。LOXL2 的表达水平在细胞上清液和 HCC 细胞系之间相似。多变量分析表明门静脉侵犯(P=0.015)、静脉侵犯(P=0.026)、血清 AFP(α-胎蛋白)水平(P=0.019)和 LOXL2 表达(P=0.009)是独立的预后因素。结果表明,较高水平的 LOXL2 可能有助于肿瘤进展,表明 LOXL2 作为 HCC 的治疗靶点具有临床价值。