Purpose: Hepatoma-derived growth factor (HDGF), which is unrelated to hepatocyte growth factor, can stimulate DNA synthesis and cell proliferation on entering the nucleus. We hypothesize that HDGF plays an important role in biologic behavior of early-stage non-small-cell lung cancer (NSCLC).

Patients and methods: Ninety-eight patients with pathologic stage I NSCLC who underwent curative surgery were studied. Immunohistochemistry was used to determine the expression level of HDGF in the tumor specimens. The intensity of the protein staining and percentage of stained tumor cells were used to determine a labeling index. Statistical analyses, all two-sided, were performed to determine the prognostic effect of HDGF expression levels on clinical parameters and outcomes.

Results: The mean +/- standard deviation HDGF labeling index in the 98 tumors was 185 +/- 41. Patients whose tumors had higher HDGF indexes (>/= 185) had a significantly poorer probability of overall survival at 5 years after surgery than did those with lower HDGF indexes (0.26 v 0.82; P <.0001). Similarly, the 5-year disease-specific and disease-free survival probabilities were lower in those with higher HDGF indexes (0.42 v 0.92, and 0.34 v 0.71; P <.0001 and P =.0008; respectively). Multivariate analysis indicated that HDGF level was an independent predictor of overall, disease-specific, and disease-free survivals.

Conclusion: Overexpression of HDGF is common in early-stage NSCLC. The expression level in tumor cells is strongly correlated with poor overall, disease-specific, and disease-free survivals, suggesting HDGF may be a powerful prognostic marker for patients with early-stage NSCLC.