title: Expression and significance of heparanase and nm23-H1 in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Surgery, Second Affiliated Hospital of Medical School of Zhejiang University, Hangzhou 310009, Zhejiang Province, China.
authors.forename: Ying-Bin
authors.initials: YB
authors.lastname: Liu
authors.forename: Shun-Liang
authors.initials: SL
authors.lastname: Gao
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Chen
authors.forename: Shu-You
authors.initials: SY
authors.lastname: Peng
authors.forename: He-Qing
authors.initials: HQ
authors.lastname: Fang
authors.forename: Yu-Lian
authors.initials: YL
authors.lastname: Wu
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Peng
authors.forename: Zhe
authors.initials: Z
authors.lastname: Tang
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Wang
authors.forename: Gui-Long
authors.initials: GL
authors.lastname: Deng
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Li
authors.forename: Xue-Dong
authors.initials: XD
authors.lastname: Feng
authors.forename: Hao-Ran
authors.initials: HR
authors.lastname: Qian
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; D005966:Glucuronidase; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D012333:RNA, Messenger; D000099175:Heparanase; C517938:NME1 protein, human