The expression of arginase-2 and its association with proliferation, apoptosis and prognosis of hepatocellular carcinoma

顾春燕; 钱　铮

doi:10.19401/j.cnki.1007-3639.2018.02.004

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The expression of arginase-2 and its association with proliferation, apoptosis and prognosis of hepatocellular carcinoma

更新时间：2026-01-27

- The expression of arginase-2 and its association with proliferation, apoptosis and prognosis of hepatocellular carcinoma
- China Oncology Vol. 28, Issue 2, Pages: 105-110(2018)
- 作者机构：
  
  南通大学附属南通第三医院病理科,江苏,南通,226006
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2018.02.004
  CLC： R735.7
- Published Online：08 March 2018，
  
  Published：08 March 2018
- 稿件说明：
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肖锋,顾春燕,钱　铮,等. 精氨酸酶2表达与肝细胞癌增殖凋亡及预后的关系研究[J]. 中国癌症杂志, 2018, 28(2): 105-110.

顾春燕, 钱　铮. The expression of arginase-2 and its association with proliferation, apoptosis and prognosis of hepatocellular carcinoma[J]. China Oncology, 2018, 28(2): 105-110.
肖锋,顾春燕,钱　铮,等. 精氨酸酶2表达与肝细胞癌增殖凋亡及预后的关系研究[J]. 中国癌症杂志, 2018, 28(2): 105-110. DOI： 10.19401/j.cnki.1007-3639.2018.02.004.

顾春燕, 钱　铮. The expression of arginase-2 and its association with proliferation, apoptosis and prognosis of hepatocellular carcinoma[J]. China Oncology, 2018, 28(2): 105-110. DOI： 10.19401/j.cnki.1007-3639.2018.02.004.

摘要

背景与目的：精氨酸酶-2(arginase-2，ARG-2)在人类多种恶性肿瘤中均可以检测到异常表达，前期的研究发现，ARG-2在肝细胞癌(hepatocellular carcinoma，HCC)组织中表达明显升高，并且ARG-2与HCC组织学分级相关。该研究拟进一步探讨ARG-2在HCC中的表达与癌细胞增殖、凋亡及预后的关系。方法：应用反转录-聚合酶链式反应(reverse transcription-polymerase chain reaction，RT-PCR)方法检测14例HCC及癌旁肝组织、14例正常肝组织中ARG-2 mRNA表达水平。免疫组织化学方法检测158例HCC患者手术切除标本的ARG-2、增殖相关蛋白Ki-67、cyclin D1以及细胞凋亡相关蛋白活化的caspase-3、caspase-8、caspase-9的表达，分析ARG-2与Ki-67、cyclin D1表达的相关性，ARG-2与活化的caspase-3、caspase-8、caspase-9的相关性；应用免疫荧光双标记方法检测ARG-2与活化的caspase-3共表达情况，ARG-2与凋亡细胞共定位情况；采用电话随访患者。结果：ARG-2 mRNA表达水平在HCC组织中明显高于癌旁和正常肝组织(F=27.10，P0.01)，ARG-2表达与Ki-67、cyclin D1表达呈正相关(分别r=0.247 8，P0.01；r=0.372 7，P0.01)；ARG-2表达与活化的caspase-3

caspase-8表达呈正相关性(分别r=0.191 0，P0.05；r=0.180 5，P0.05)，而与caspase-9表达无明显相关性(γ=0.108 9，P0.05)；免疫荧光双标记显示ARG-2与活化的caspase-3有共表达，并且与凋亡细胞有共定位。Kaplan-Meier生存曲线显示，ARG-2(-)组患者中位生存时间为32个月，ARG-2(+)组中位生存时间为18个月，ARG-2(++)组中位生存时间为15个月，log-rank检验结果显示，各组间差异有统计学意义，ARG-2(-)组高于ARG-2(+)、ARG-2(++)组( χ

=12.278，P0.01)。结论：ARG-2可能参与调节HCC癌细胞增殖、凋亡过程；检测HCC组织中ARG-2的表达可以提示预后。

Abstract

Background and purpose: Abnormal expression of arginase 2 (ARG2) in a variety of human malignant tumors was detected. Previous studies found that ARG2 significantly increased in hepatocellular carcinoma (HCC) and was related to histological grading of HCC. This study aimed to analyze the association of ARG2 expression with cell proliferation

apoptosis and prognosis in HCC. Methods: The expression levels of ARG2 mRNA in 14 samples of HCC

paracancerous liver tissues and 14 samples of normal liver were detected by reverse transcriptionpolymerase chain reaction (RT-PCR). Tissue sections from 158 HCC patients were examined immunohistochemically for protein expression of ARG2

proliferation-related proteins (Ki-67 and cyclin D1) and apoptosis-related proteins (activated caspase-3

caspase-8 and caspase-9). Immunofluorescence double labeling method was used to detect the coexpression of ARG2 and activated caspase-3

and the colocalization between ARG2 and apoptotic cells. Patients were followed up by telephone. Results: TThe expression of ARG2 mRNA was significantly increased in HCC compared with the paracancerous liver tissues and normal liver tissues (F=27.10

P0.01). The expression of ARG2 was positively correlated with the expression of Ki-67 and cyclin D1

respectively (r=0.247 8

P0.01; r=0.372 7

P0.01). The expression of ARG2 was positively correlated with the expression of activated caspase-3 and caspase-8

respectively (r=0.191 0

P0.05; r=0.180 5

P0.05)

but not with the caspase-9 (r=0.108 9

P0.05). Immunofluorescence double labeling showed that ARG2 was coexpressed with the activated caspase-3 and colocalized with apoptotic cells. Kaplan-Meier survival curves showed that the median survival time was 32 months in ARG2(-) group

18 months in ARG2(+) group and 15 months in ARG2(++) group. The log-rank test results showed that there were significant differences in median survival time between the groups

and the median survival time in ARG2(-) group was longer than

that in ARG2(+) and ARG2(++) groups (χ

=12.278

P0.01). Conclusion: ARG2 may be involved in regulating the proliferation and apoptosis of HCC cancer cells. Detecting the expression of ARG2 in HCC tissues may indicate prognosis.

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