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Expression of Hepatoma-Derived Growth Factor Is a Strong Prognostic Predictor for Patients With Early-Stage Non–Small-Cell Lung Cancer

From the Department of Thoracic/Head and Neck Medical Oncology, Departments of Biostatistics, Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Department of Pediatrics, The Johns Hopkins University, School of Medicine, Baltimore, MD

Address reprint requests to Li Mao, MD, Department of Thoracic/Head and Neck Medical Oncology, Unit 432, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: lmao{at}mdanderson.org

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.

Supported in part by Department of Defense Grant DAMD17-01-1-0689-1; and National Cancer Institute Grants PO1 CA91844, UO1 CA86390, and P30 CA 16620.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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