title: LOXL4 is downregulated in hepatocellular carcinoma with a favorable prognosis.
abstract: 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.
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Mengxin
authors.initials: M
authors.lastname: Tian
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Weiren
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Xifei
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Liuxiao
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Zhenbin
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Yuanfei
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Shuangjian
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Dai
authors.affiliation: 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.
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D008249:Protein-Lysine 6-Oxidase; D034741:RNA, Small Interfering; D015996:Survival Rate
chemical_list: D034741:RNA, Small Interfering; D000594:Amino Acid Oxidoreductases; C445682:LOXL4 protein, human; D008249:Protein-Lysine 6-Oxidase
keywords: Lysyl oxidase like 4; hepatocellular carcinoma; immunohistochemistry; prognosis