Clinical value of apoptosis and angiogenesis factors in estimating the prognosis of hepatocellular carcinoma.
OBJECTIVE
Whereas some studies have indicated that the prognosis of hepatocellular carcinoma (HCC) was correlated to some apoptosis and angiogenesis factors: p53, survivin, matrix metalloproteinases (MMPs, including MMP-2 and MMP-9) and vascular endothelial growth factor (VEGF), other studies have failed to confirm this. The aim of the present study is to investigate the expression of p53, survivin, MMPs and VEGF in HCC and the relationship between these factors and the prognosis of HCC patients.


METHODS
The expression of p53, survivin, MMP-2, MMP-9 and VEGF was measured by immunohistochemical assays in the liver resection specimens of 90 patients with HCC.


RESULTS
The positive rate of p53, survivin, MMP-2, MMP-9 and VEGF was 33.3, 51.1, 60.0, 37.8 and 76.7%, respectively. The expression of MMP-2, MMP-9 and VEGF was correlated to the recurrence of HCC patients, respectively (P < 0.01). No correlation was found between the expression of apoptosis factors (p53 and survivin) and the recurrence of HCC patients, respectively (P > 0.05). The positive correlations were found between MMP-2 and VEGF (r = 0.32, P < 0.01), MMP-9 and VEGF (r = 0.24, P < 0.05). Significant differences of disease-free survival rates occurred among subgroups according to the expression of MMP-2, MMP-9 and VEGF (P < 0.01). Multivariate analysis revealed that macroscopically disseminated nodules, tumor micrometastasis, high serum alpha-fetoprotein level, positive expression of MMP-9 and VEGF were independent recurrence risk factors.


CONCLUSIONS
Our investigation revealed that p53 and survivin could not estimate the prognosis of HCC patients. Angiogenesis factors (MMPs and VEGF) positively correlated to the prognosis of HCC patients. The expression of MMPs and VEGF in HCC tissues could be regarded as a valuable indicator in estimating the prognosis of HCC patients.
Guo
Rong-Ping
RP
State Key Laboratory of Oncology in Southern China, 651 Dongfeng Road East, Guangzhou, 510060, China. guorongp@mail.sysu.edu.cn
Zhong
Chong
C
Shi
Ming
M
Zhang
Chang-Qing
CQ
Wei
Wei
W
Zhang
Ya-Qi
YQ
Li
Jin-Qing
JQ
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D015996:Survival Rate; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases