Significance of Lysyl oxidase-like 2 gene expression on the epithelial-mesenchymal status of hepatocellular carcinoma

Go Ninomiya, Suguru Yamada*, Masamichi Hayashi, Shigeomi Takeda, Masaya Suenaga, Hideki Takami, Mitsuro Kanda, Naoki Iwata, Yukiko Niwa, Chie Tanaka, Daisuke Kobayashi, Tsutomu Fujii, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2664-2672
Number of pages9
JournalOncology Reports
Volume39
Issue number6
DOIs
StatePublished - 2018/06

Keywords

  • Epithelial-to-mesenchymal transition
  • Hepatocellular carcinoma
  • LOX
  • LOX family
  • LOXL2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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