Clinical Implications of Lysyl Oxidase-Like Protein 2 Expression in Pancreatic Cancer

赖氨酰氧化酶样蛋白 2 在胰腺癌中的表达及其临床意义

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作者:Nobutake Tanaka, Suguru Yamada, Fuminori Sonohara, Masaya Suenaga, Masamichi Hayashi, Hideki Takami, Yukiko Niwa, Norifumi Hattori, Naoki Iwata, Mitsuro Kanda, Chie Tanaka, Daisuke Kobayashi, Goro Nakayama, Masahiko Koike, Michitaka Fujiwara, Tsutomu Fujii, Yasuhiro Kodera

Abstract

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.

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