The expression of arginase-2 and its association with proliferation, apoptosis and prognosis of hepatocellular carcinoma / 中国癌症杂志

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, P＜0.01). The expression of ARG2 was positively correlated with the expression of Ki-67 and cyclin D1, respectively (r=0.247 8, P＜0.01; r=0.372 7, P＜0.01). The expression of ARG2 was positively correlated with the expression of activated caspase-3 and caspase-8, respectively (r=0.191 0, P＜0.05; r=0.180 5, P＜0.05), but not with the caspase-9 (r=0.108 9, P＞0.05). 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 (χ2=12.278, P＜0.01). 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.