[Study on the prognostic value of hepatocyte growth factor and c-met for patients with hepatocellular carcinoma].
OBJECTIVE
To analyze the prognostic value of hepatocyte growth factor (HGF) and c-met for patients with hepatocellular carcinoma (HCC) after hepatectomy.


METHODS
Twenty-five patients undergoing partial hepatectomy for HCC were studied. Serum HGF level was determined using ELISA kit before and after operation respectively. c-met protein and mRNA expression in cancerous and paracancerous tissues were detected by immunohistochemical and RT-PCR methods respectively. The correlations of clinical-pathologic parameters with the HGF level in serum and c-met expression in cancerous tissue were analyzed respectively.


RESULTS
HCC patients had a significantly higher concentration of serum HGF than normal controls and chronic hepatitis B respectively [(1.03 +/- 0.09) ng/ml vs (0.69 +/- 0.02) ng/ml and (0.74 +/- 0.09) ng/ml]. No significant difference in serum HGF was observed between HCC and cirrhosis patients with Child-Pugh score B/C [(1.03 +/- 0.09) ng/ml vs (1.04 +/- 0.11) ng/ml]. Serum HGF concentrations were positively correlated with tumor size (> 5 cm), node cirrhosis, portal vein tumor thrombi (PVTT) and preoperative alpha-fetoprotein (AFP) level (> or = 400 microg/L). After the resection of tumor, serum HGF concentration had a peak on the third postoperative day (POD), and then declined, but did not return to normal level on the tenth POD. From preoperative day to third POD, HGF concentration had a higher elevation in patients with major resection than with local resection. Moderately or strongly positive expression of c-met protein was observed in 21 cancerous regions (21/25), and only in 5 paracancerous regions. The intensive expression of c-met mRNA was 100% (25/25) detectable in the cancerous tissues, but only 24% (6/25) in the paracancerous tissues. The expression extent of c-met protein was correlated with portal vein tumor thrombi (PVTT). In paracancerous tissues, the expression of c-met protein was more intense in patients with cirrhosis than those without cirrhosis. The patients with recurrence or metastases after operation had a higher level of serum HGF and more intensive expression of c-met than other patients. No significant association was observed between HGF in serum and c-met expression in cancerous tissue.


CONCLUSIONS
The over-expression of HGF and its receptor c-met indicate an adverse prognosis for HCC patients. The sustained high level of serum HGF after hepatectomy may be a factor related to early tumor recurrence and metastasis.
Wu
Fu-sheng
FS
Department of Surgical Oncology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Zheng
Shu-sen
SS
Wu
Ling-jiao
LJ
Ding
Wei
W
Ma
Zhi-min
ZM
Wang
Zhao-ming
ZM
Teng
Li-song
LS
Zhao
Wen-he
WH
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met