The clinical significance of hepatocyte growth factor for non–small cell lung cancer

Abstract

Background. Hepatocyte growth factor (HGF) is a cytokine that is released after injury. It is a paracrine factor that is produced by mesenchymal cells; epithelial and endothelial cells respond to HGF through its receptor, the c-met protein. Hepatocyte growth factor induces cell growth and cell movement and is also highly angiogenic. Evidence from breast cancer patients suggests that HGF is a negative prognostic indicator for breast cancer and is associated with invasive disease.Methods. We measured the HGF content in tumor tissue from 56 non–small cell lung cancer patients using the Western blot technique. The amount of HGF in tumor extracts was quantitated by densitometry after transfer of proteins to nitrocellulose and exposure to antibodies. Survival curves were generated based on clinical information obtained for each patient.Results. Our data indicate that HGF is also a negative prognostic indicator in lung cancer. As in the study of breast cancer patients, HGF was associated with recurrence and poor survival; the relative risk was seen to increase with increasing HGF tumor content. At levels of HGF greater than 100 units, the relative risk was 10, compared with that in patients with an HGF level of 1 unit. Node-negative patients with an elevated HGF tumor content had a significantly poorer outcome than node-positive patients with a low HGF tumor content. The same relationship was observed if the patients were stratified by stage: elevated HGF was associated with stage I patients whose disease recurred and who died of their disease, and stage I patients with elevated HGF had a worse survival than higher stage patients with a low level of HGF.Conclusions. These results suggest that elevated HGF may predict a more aggressive biology in non–small cell lung cancer patients. The level of HGF may be useful as an indicator of high risk in early stage lung cancer patients.