Alterations of oncogenes, tumor suppressor genes and growth factors in hepatocellular carcinoma: with relation to tumor size and invasiveness.
OBJECTIVE
To make a better understanding of the molecular mechanisms involved in recurrence and metastasis of the hepatocellular carcinoma (HCC), some invasion related oncogenes, and growth factors have been investigated.


METHODS
The studies were separately carried out, the results of which were summarized in this article with relation to tumor size and invasiveness of HCC.


RESULTS
The aberration rates of p53 and CDKN2 in HCC were 45.9% and 36.4% respectively, which were higher in invasive HCC compared with non-invasive HCC. H-ras expression was positive in 29.3% of HCC, which was associated with recurrence and extrahepatic metastasis of HCC. Intralesional injection of H-ras antisense gene markedly inhibited the tumor growth and metastasis of HCC in nude mice. The positive rates of transforming growth factor (TGF)-alpha, epidermal growth factor receptor (EGFR) and c-erbB-2 were 45.7%, 47.1% and 92.3% respectively. The expression of EGFR was closely related to TGF-alpha, which was related to HCC recurrence. But no obvious difference of TGF-alpha or c-erbB-2 expression was found between HCC with and without recurrence, or with and without extrahepatic metastasis. Expression of nm23/tissue inhibitor of metalloproteinase (TIMP)-2 was positively associated with the prognosis of HCC patients (Log-rank, P < 0.001). The alterative rates of above-mentioned genes and growth factors in small HCC were slightly lower than that in large ones, but no significant difference was shown except the p53 mutation.


CONCLUSIONS
The p53/CDKN2 mutation, over-expression of H-ras/EGFR, were associated with the invasiveness and recurrence of HCC. H-ras antisense gene might be of potential implication in the control of HCC recurrence and metastasis. Expression of nm23/TIMP-2 was closely related to the prognosis of HCC patients. Biological characteristics remained critical points to the prognosis even in small HCC.
Tang
Z
Z
Liver Cancer Institute, Shanghai Medical University, China.
Qin
L
L
Wang
X
X
Zhou
G
G
Liao
Y
Y
Weng
Y
Y
Jiang
X
X
Lin
Z
Z
Liu
K
K
Ye
S
S
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D018773:Genes, erbB-1; D019942:Genes, p16; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D020559:Monomeric GTP-Binding Proteins; D009154:Mutation; D054778:NM23 Nucleoside Diphosphate Kinases; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009701:Nucleoside-Diphosphate Kinase; D014157:Transcription Factors / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000378:metabolism
D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins