Expression of hepatocyte growth factor and c-Met in non-small-cell lung cancer and association with lymphangiogenesis

Previous experimental studies have demonstrated that hepatocyte growth factor (HGF) and its receptor c‑Met serve an important function in lymphangiogenesis, but their biological functions in malignant tumors have remained elusive. The present study aimed to investigate the expression patterns of HGF‑α and c‑Met and their association with vascular endothelial growth factor (VEGF)‑C, lymphatic vessel density and lymph node metastasis in non‑small‑cell lung cancer (NSCLC). In the present study, the lymphatic microvessel density (LMVD) and the expression levels of HGF‑α, its receptor c‑Met and VEGF‑C were determined in 113 human NSCLC tissues and 113 normal lung tissue samples, using immunohistochemical staining. As a result, it was determined that the expression levels of HGF‑α, c‑Met and VEGF‑C were significantly higher in NSCLC tissues than those in normal lung tissues (HGF‑α, 67.3 vs. 20.4%, P<0.001; c‑Met, 74.3 vs. 23.0%, P<0.001; and VEGF‑C, 65.5 vs. 23.9%, P<0.001). HGF‑α expression was observed to be significantly associated with that of VEGF‑C (r=0.234, P=0.012) or c‑Met (r=0.648, P<0.001). In addition, there was a positive correlation between the expression levels of VEGF‑C and c‑Met (r=0.224, P=0.017). In NSCLC tissues, the expression of HGF‑α, c‑Met or VEGF‑C was significantly correlated with the LMVD (P=0.045, 0.002 and 0.001, respectively), and lymph node metastasis was more common in HGF‑α, c‑Met or VEGF‑C‑positive groups (P=0.020, 0.020 and 0.009, respectively). In addition, the HGF‑α or VEGF‑C‑positive groups presented shorter survival time periods. In conclusion, the expression of HGF‑α or c‑Met was closely correlated with VEGF‑C, LMVD and metastases of lymph nodes, indicating that HGF‑α, c‑Met and VEGF‑C may perform important and collaborative actions in lymphangiogenesis and lymphatic metastasis of primary NSCLC.