[The expression and significance of heparanase and nm23-H1 in hepatocellular carcinoma].
OBJECTIVE
To explore the relation between heparanase (HPA) and nm23-H1 in hepatocellular carcinoma (HCC), and judge whether they may be used as valuable markers in predicting postoperative metastasis and recurrence of HCC.


METHODS
Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (S-P method) were used to measure the expressions of the HPA mRNA and nm23-H1 protein in the primary tumor tissue and paracancer tissue of 33 cases of HCC. The paracancer tissues of 9 cases of benign liver tumor were used as normal controls. The results were analyzed in combination with the results of clinicopathological examination and follow-up.


RESULTS
The expression of HPA gene was positive in 16 cases of primary tumor tissues of HCC with a positive rate of 48.5%, significantly higher than those in paracancer tissues of HCC cases and in normal controls (P < 0.01). The HPA expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state and cirrhosis of liver. The positive rates of HPA mRNA in the group with high tendency to metastasis or recurrence and the group with metastasis or recurrence during follow-up were significantly higher than that in the group with low tendency to metastasis or recurrence group (P < 0.05) and that in the group without metastasis or recurrence (P < 0.01). The poorly differentiated tumor and tumor of TNM stage III-IV had higher positive rates of HPA gene expression than the well-mediate differentiated tumor and tumor of TNM stage I-II (P < 0.05). The positive expression rates of nm23-Hl protein in HCC tissue was significantly lower than that in corresponding non-cancerous or normal liver tissue (P < 0.05). nm23-Hl expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state, cirrhosis of liver, Edmondson grade, and TNM stage (P > 0.05). The positive rate of nm23-Hl in the group with high tendency to metastasis and recurrence and in patients with metastasis or recurrence during follow-up was obviously higher than that in the group with low tendency to metastasis and recurrence (P = 0.018) and that in the patients without metastasis and recurrence (P = 0.024), but no significant difference was found between HPA positive and negative groups (P = 0.082). According to the results of follow-up, the rates of accuracy in predicting metastasis of positive HPA, negative nm23-H1 and combination of positive HPA with negative nm23-H1 were 78.6% (11/14), 68.8% (11/16) and 88.9% (8/9) respectively.


CONCLUSIONS
Expression of HPA and/or nm23-Hl are related with metastasis and recurrence of HCC. Combining the expression rate of HPA with the expression rate of nm23-H1 may increase the accuracy in predicting HCC postoperative metastasis and recurrence.
Liu
Yingbin
Y
Department of Surgery, Second Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310009, China.
Chen
Xiaopeng
X
Peng
Shuyou
S
Fang
Heqing
H
Wu
Yulian
Y
Peng
Chenhong
C
Shi
Liubin
L
Bai
Mingdong
M
Xu
Bin
B
Wang
Jianwei
J
Deng
Guilong
G
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis*; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis*; D000099175:Heparanase
D005966:Glucuronidase; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D012333:RNA, Messenger; D014157:Transcription Factors; D000099175:Heparanase; C517938:NME1 protein, human