Increase in the circulating level of hepatocyte growth factor in gastric cancer patients

Abstract

Summary We measured serum concentrations of hapatocyte growth factor (HGF) in patients with gastric cancer and compared these with the histological findings and conventional tumour markers, including CEA, CA19-9 and CA125, for evaluation of the significance of serum HGF levels as a tumour marker. The HGF levels were measured by an enzyme-linked immunosorbent assay (ELISA) system. The average levels of serum HGF in 89 healthy control subjects, 104 patients with primary gastric cancer and 15 patients with recurrent gastric cancer were 0.31 ± 0.11 ng ml-1, 0.42 ± 0.50 ng ml-1 and 0.92 ± 0.39 ng mi-1 respectively. The average level in patients with recurrent disease was significantly higher than in healthy control subjects and in primary cancer patients (P< 0.001 and P< 0.003 respectively). Of 104 patients with primary gastric cancer, 35 (33.7%) showed an aberrant increase in the circulating level of HGF. The increased HGF levels were significantly associated with the degrees of histological tumour invasion and venous invasion. Of 15 patients with recurrent gastric cancer, 14 (93.3%) showed an aberrant increase. No correlation was found between serum HGF levels and CEA levels, CA19-9 levels and CA125 levels. However, the rate of the aberrant increase in HGF levels was significantly higher than that of any other tumour markers, including CEA, CAl 9-9 and CAl 25, in primary gastric cancer patients. In conclusion, the circulating levels of HGF were elevated in approximately one-third of patients with primary gastric cancer, particularly in those with high grades of histological tumour invasion and venous invasion, and frequently in patients with distant metastases, suggesting that HGF might play important roles in the tumour progression of gastric cancer. Furthermore, serum HGF levels may be of value as a tumour marker in patients with gastric cancer.

Role of HGF/c-met system in invasion and metastasis of oral squamous cell carcinoma cellsin vitro and its clinical significance

“…Several investigators reported that serum HGF levels in cancer patients were increased significantly when compared with those in healthy volunteers. [21][22][23] Serum HGF levels in the patients were reported to be affected by liver injury or renal disease. 35,36 All of the patients included in this experiment showed normal liver function and kidney function, however, and did not exhibit any severe inflammation of other organs.…”

“…18 It was reported that HGF induced tyrosine phosphorylation of focal adhesion kinase, p125FAK, 19 and promoted the migration and invasion of oral SCC cells. 20 Moreover, in several clinical studies, a relationship between the concentration of HGF in serum or in cancer tissue and the progression of disease has been noted in patients with gastric cancer, 21 breast cancer 22 and lung cancer, 23 but has not been reported in patients with oral cancer.…”

Metastatic squamous cell carcinoma cells that overexpress c-Met exhibit enhanced angiogenesis factor expression, scattering and metastasis in response to hepatocyte growth factor

“…Yu et al recently showed that a nonautocrine interaction between HGF transgenic hosts and c-Met expressing melanoma cells significantly promotes tumor metastasis in vivo (Yu and Merlino, 2002). Clinically, elevated serum HGF levels have been found in patients with cancers from bladder, breast, colon, gastric, liver, lung and head and neck (Takigawa et al, 1997;Taniguchi et al, 1997;Fukuura et al, 1998;Toi et al, 1998;Junbo et al, 1999;Gohji et al, 2000;Naughton et al, 2001;Uchida et al, 2001, Dong, 2001b. Significantly, this elevated serum HGF is associated with poor prognosis.…”

Increased hepatocyte growth factor in serum in acute graft-versus-host disease

“…Serum HGF concentrations have been reported to be elevated in liver disease, chronic renal failure, systemic inflammatory response syndrome (SIRS), and malignant diseases such as leukemia, breast cancer, and gastric cancer. [17][18][19][20] Circulating HGF is increased in the presence of septic complications. Sakon et al 21 reported that HGF in serum was elevated in patients with sepsis, and also correlated with CRP in patients with nonseptic SIRS.…”