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犬尿氨酸3-单加氧酶的预后意义及其对人肝细胞癌增殖、迁移和侵袭的影响

Prognostic significance of kynurenine 3-monooxygenase and effects on proliferation, migration, and invasion of human hepatocellular carcinoma.

作者信息

Jin Haojie, Zhang Yurong, You Haiyan, Tao Xuemei, Wang Cun, Jin Guangzhi, Wang Ning, Ruan Haoyu, Gu Dishui, Huo Xisong, Cong Wenming, Qin Wenxin

机构信息

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine.

Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University.

出版信息

Sci Rep. 2015 Jun 23;5:10466. doi: 10.1038/srep10466.

Abstract

Kynurenine 3-monooxygenase (KMO) is a pivotal enzyme in the kynurenine pathway of tryptophan degradation and plays a critical role in Huntington's and Alzheimer's diseases. This study aimed to examine the expression of KMO in human hepatocellular carcinoma (HCC) and investigate the relationship between its expression and prognosis of HCC patients. We first analyzed KMO expression in 120 paired HCC samples (HCC tissues vs matched adjacent non-cancerous liver tissues), and 205 clinical HCC specimens using immunohistochemistry (IHC). Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC. The results of IHC analysis showed that KMO expression was significantly higher in HCC tissues than that in normal liver tissues (all p < 0.05). Survival and recurrence analyses showed that KMO was an independent prognostic factor for overall survival (OS) and time to recurrence (TTR) (both p<0.01). And in vitro studies revealed that KMO positively regulated proliferation, migration, and invasion of HCC cells. These results suggest that KMO exhibits tumor-promoting effects towards HCC and it may serve as a novel prognostic marker in HCC.

摘要

犬尿氨酸3-单加氧酶(KMO)是色氨酸降解犬尿氨酸途径中的关键酶,在亨廷顿病和阿尔茨海默病中起关键作用。本研究旨在检测KMO在人肝细胞癌(HCC)中的表达,并探讨其表达与HCC患者预后的关系。我们首先采用免疫组织化学(IHC)方法分析了120对HCC样本(HCC组织与配对的癌旁非癌肝组织)以及205例临床HCC标本中KMO的表达。采用Kaplan-Meier生存分析和Cox回归分析评估HCC的预后。IHC分析结果显示,HCC组织中KMO的表达显著高于正常肝组织(所有p<0.05)。生存和复发分析表明,KMO是总生存期(OS)和复发时间(TTR)的独立预后因素(均p<0.01)。体外研究表明,KMO对HCC细胞的增殖、迁移和侵袭具有正向调节作用。这些结果表明,KMO对HCC具有促肿瘤作用,可能作为HCC的一种新的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8f/4479133/cd03a62d1644/srep10466-f1.jpg

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