Effect of hepatocyte growth factor on progression of liver metastasis in colorectal cancer.
OBJECTIVE
Colorectal cancer (CRC) is one of the most common cancers worldwide, and a strategy to assess and control liver metastasis will be critical to control patient prognosis. To evaluate therapeutic approaches, the biological responses associated with hepatectomy were studied with a focus on hepatocyte growth factor (HGF).


METHODS
In 54 patients with metastatic liver tumors due to CRC, c-Met expression was estimated by western blotting from resected tissue specimens. Serum HGF levels were measured by an ELISA method and compared with other liver function serum factors.


RESULTS
The preoperative serum level of HGF was found to be related to ICGR15, ALP, CHE and AST, but after hepatectomy, the change was not correlated with other liver function factors. From an evaluation of pre-operative liver condition using ICGR15, an increasing rate (post/pre) of AST, ALT, ALP and HGF was observed to be higher in cases with positive outcomes. In cases with normal pre-operative levels of serum HGF, the increasing rate (post/pre) of HGF after surgery was higher than in cases with abnormally high pre operative values (3.07 +/- 0.87 and 2.38 +/- 0.74, respectively; p = 0.0102). In cases where tumors recurred within 6 months (early recurrence cases), the c-Met value in tumor tissue was higher than in cases with no recurrence, even in cases where there was no tendency for an increasing rate of HGF. In addition, multiplying data serum HGF increasing rate by c-Met value in tissue was significantly higher in early recurrence cases than in cases with no recurrence, (3.96 +/- 0.62 and 3.00 +/- 1.16 respectively; p = 0.0135). A similar finding was also detected following curative operations involving multiple tumor resection (3.93 +/- 0.64 vs. 2.84 +/- 1.24 for early and no recurrence, respectively; p = 0.0147).


CONCLUSIONS
The present study demonstrated that cancer with high c-Met expression and under high level of its ligand, HGF, led to recurrence soon after hepatectomy, leading to unfavorable patient prognosis. If pathological or biochemical factors from resected specimens could help identify patients with a high risk of relapse, innovative adjuvant chemotherapy protocols could be initiated.
Osada
Shinji
S
Surgical Oncology, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. sting@gifu-u.ac.jp
Matsui
Satoshi
S
Komori
Shuji
S
Yamada
Junko
J
Sanada
Yuichi
Y
Ihawa
Aiko
A
Tanaka
Yoshihiro
Y
Tokuyama
Yasuharu
Y
Okumura
Naoki
N
Nonaka
Kenichi
K
Hosono
Yoshiki
Y
Takahashi
Takao
T
Yamaguchi
Kazuya
K
Yoshida
Kazuhiro
K
D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D000637:Transaminases / Q000378:metabolism; D016896:Treatment Outcome
C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; D000637:Transaminases; D019859:Proto-Oncogene Proteins c-met