Tian Mengxin, Liu Weiren, Jin Lei, Jiang Xifei, Yang Liuxiao, Ding Zhenbin, Shen Yinghao, Peng Yuanfei, Gao Dongmei, Li Lixin, Zhou Jian, Qiu Shuangjian, Dai Zhi, Fan Jia, Shi Yinghong
Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China ; Institutes of Biomedical Sciences, Fudan University Shanghai, People's Republic of China.
Int J Clin Exp Pathol. 2015 Apr 1;8(4):3892-900. eCollection 2015.
Lysyl oxidase like 4 (LOXL4), a member of the secreted copper-dependent amine oxidases that contribute to the assemble and maintenance of the extracellular matrix (ECM), was found to be up-regulated or down-regulated in different cancer types, suggesting its paradoxical roles in cancer. The specific role of LOXL4 in hepatocellular carcinoma (HCC), however, is still yet to be defined. Twenty-eight pairs of HCC specimens were used for LOXL4 mRNA expression analysis. The mRNA expression in HCC cell lines was examined, and HepG2 was selected for LOXL4 small interfering RNA (siRNA) interference to investigate the biological function of LOXL4, LOXL4 immunohistochemical staining was performed using a tissue microarray containing 298 HCC patients. The prognostic and diagnostic value of LOXL4 was evaluated using Cox regression and Kaplan-Meier analysis. LOXL4 mRNA or protein expression was significantly lower in HCC tissues than peritumoral tissues (LOXL4 mRNA expression, P = 0.018; LOXL4 protein expression, P < 0.001). Low LOXL4 expression was associated with lower overall survival (OS) rates and higher cumulative recurrence rates. Multivariate analysis indicated that LOXL4 was an independent prognostic indicator for OS and time to recurrence (TTR). Our results revealed that LOXL4 was down-regulated in HCC and correlated with aggressive tumors and a worse clinical outcome. LOXL4 may be a potential biomarker to identify the HCC patients with a higher risk of recurrence.
赖氨酰氧化酶样4（LOXL4）是分泌型铜依赖性胺氧化酶家族的成员，有助于细胞外基质（ECM）的组装和维持。研究发现，LOXL4在不同类型的癌症中表达上调或下调，提示其在癌症中具有矛盾的作用。然而，LOXL4在肝细胞癌（HCC）中的具体作用仍有待确定。本研究使用28对HCC标本进行LOXL4 mRNA表达分析，检测了HCC细胞系中的mRNA表达，并选择HepG2细胞进行LOXL4小干扰RNA（siRNA）干扰，以研究LOXL4的生物学功能。使用包含298例HCC患者的组织芯片进行LOXL4免疫组织化学染色，采用Cox回归和Kaplan-Meier分析评估LOXL4的预后和诊断价值。结果显示，HCC组织中LOXL4 mRNA或蛋白表达显著低于癌旁组织（LOXL4 mRNA表达，P = 0.018；LOXL4蛋白表达，P < 0.001）。低LOXL4表达与较低的总生存率（OS）和较高的累积复发率相关。多因素分析表明，LOXL4是OS和复发时间（TTR）的独立预后指标。我们的研究结果表明，LOXL4在HCC中表达下调，与侵袭性肿瘤和较差的临床结局相关。LOXL4可能是识别复发风险较高的HCC患者的潜在生物标志物。
