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 whether they could be used as valuable markers in predicting post-operative metastasis and recurrence of HCC.


METHODS
Reverse transcription-polymerase chain reaction and immunohistochemistry (S-P method) were used to measure the expressions of HPA mRNA and nm23-H1 protein in primary tumor tissue and paracancerous tissue of 33 cases of HCC. Paracancerous 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 positive expression of HPA gene was significantly higher in primary tumor tissues of HCC (48.5%, 16/33) as compared to the paracancerous tissues of HCC and normal controls (3.03%, 1/33) (P < 0.01). 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 in the group with metastasis or recurrence during the follow-up were significantly higher than those in the group with low tendency to metastasis or recurrence (62.5% vs 37.5%, P < 0.05) and in the group without metastasis or recurrence (78.6% vs 21.4%, P < 0.01). The poorly differentiated tumor and tumor of TNM stages III-IV had a higher positive rate of HPA gene expression than the well differentiated tumor and tumor of TNM stages I-II (66.7% vs 33.3%, P < 0.05). The positive expression rate of nm23-H1 protein in HCC tissue was significantly lower than that in corresponding non-cancerous or normal liver tissue (45.5, 72.7, 88.9%, P < 0.05). nm23-H1 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 rates of nm23-H1 in the group with high tendency to metastasis and recurrence and in patients with metastasis or recurrence during the follow-up were obviously higher than those in the group with low tendency to metastasis and recurrence (P = 0.018) and 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 rate of accuracy in predicting metastasis of positive HPA, negative nm23-H1 and combination of positive HPA with negative nm23-H1 was 78.6% (11/14), 68.8% (11/16) and 88.9% (8/9), respectively.


CONCLUSIONS
Expression of HPA and/or nm23-H1 is related with metastasis and recurrence of HCC. Detection of the expression rate of HPA and nm23-H1 may help increase the accuracy in predicting post-operative metastasis and recurrence of HCC.
Liu
Ying-Bin
YB
Department of Surgery, Second Affiliated Hospital of Medical School of Zhejiang University, Hangzhou 310009, Zhejiang Province, China.
Gao
Shun-Liang
SL
Chen
Xiao-Peng
XP
Peng
Shu-You
SY
Fang
He-Qing
HQ
Wu
Yu-Lian
YL
Peng
Cheng-Hong
CH
Tang
Zhe
Z
Xu
Bin
B
Wang
Jian-Wei
JW
Deng
Gui-Long
GL
Li
Hai-Jun
HJ
Feng
Xue-Dong
XD
Qian
Hao-Ran
HR
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000556:secondary* / Q000601:surgery; D005260:Female; D016147:Genes, Tumor Suppressor; D005966:Glucuronidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics* / Q000378:metabolism; D011183:Postoperative Complications; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D000099175:Heparanase
D014408:Biomarkers, Tumor; D005966:Glucuronidase; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D012333:RNA, Messenger; D000099175:Heparanase; C517938:NME1 protein, human