The relationship between EGFR gain and VHL loss in lung adenocarcinoma and poor patient survival.

BACKGROUND

The prognosis of lung cancer remains poor and clinically applicable prognostic markers have not yet been satisfactory identified. Several chromosomal copy number alterations (CNAs) have been associated with metastasis, relapse, and survival of patients with lung cancer; however, no study has focused exclusively on identifying CNAs at a gene level. The aim of this study was to identify genes whose CNAs are associated with survival of patients with lung adenocarcinoma.

METHODS

The CNA status of a panel of 48 genes was detected by high-resolution array comparative genomic hybridization in 56 lung adenocarcinoma samples. The follow-up time of these patients was 8.5-65.7 months. The gene CNAs were analyzed for their association with patient survival.

RESULTS

Cox univariate regression analysis revealed that EGFR gain (hazard ratio (HR) 3.84, 95% confidence interval (CI) 1.62-9.10), VHL loss (HR 4.56, 95% CI 1.85-11.27) and WWOX loss (HR 4.14, 95% CI 1.60-10.69) were each associated with poor survival. Multivariate analyses including EGFR gain, VHL loss and WWOX loss, as well as the clinicopathological variables such as age, sex, tumor size, tumor differentiation and TNM stage showed that EGFR gain (HR 4.63, 95% CI 1.69-12.7) and VHL loss (HR 4.82, 95% CI 1.41-16.43) were independent prognostic factors for poor survival, whereas WWOX loss lost statistical significance.

CONCLUSION

These findings suggest that EGFR gain and VHL loss are associated with poor overall survival for lung adenocarcinoma patients and may be used as prognostic markers.