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.