Association of Nuclear YB-1 Localization With Lung Resistance-related Protein and Epidermal Growth Factor Receptor Expression in Lung Cancer

Nuclear Y-box binding protein 1 (YB-1) expression significantly correlated with positive lung resistance-related protein (LRP) and epidermal growth factor receptor (EGFR) expression. Tumors positive for nuclear YB-1 and LRP had a significantly worse prognosis, and those positive for nuclear YB-1 and EGFR had a significantly worse prognosis as well. Downregulation of YB-1 with small interfering RNA demonstrated an association of these factors in vitro. Thus, YB-1, LRP, and EGFR expression are of prognostic significance in non-small-cell lung cancer. Background: Y-box binding protein 1 (YB-1) is an oncogenic transcription factor that is activated in response to various genotoxic stresses. The purpose of this study was to elucidate whether YB-1 correlates with the expression of lung resistance-related protein (LRP) and epidermal growth factor receptor (EGFR) in primary lung cancer. Patients and Methods: One hundred and five non-small-cell lung cancer (NSCLC) specimens were analyzed by immunohistochemistry. Knockdown of YB-1 messenger RNA by small interfering RNA(siRNA) was tested for the lung cancer cell lines A549 and Calu-3. Results: Nuclear YB-1 expression significantly correlated with positive LRP and EGFR expression (P < .001). Nuclear YB-1 expression and positive LRP and EGFR expression were independent adverse prognostic factors in patients with NSCLC. Furthermore, patients with tumors positive for nuclear YB-1 and LRP had a significantly worse prognosis than those negative for nuclear YB-1 and LRP (P < .001). In addition, patients with tumors positive for nuclear YB-1 and EGFR had a significantly worse prognosis than those negative for nuclear YB-1 and EGFR (P < .001). In in vitro analyses that use the NSCLC cell lines A549 and Calu-3, the downregulation of YB-1 with siRNAs drastically decreased the expression of EGFR. However, downregulation of YB-1 remarkably decreased the expression of LRP in A549 cells; however, a slight decrease in LRP was induced by the downregulation of YB-1 in Calu-3 cells. Conclusion: Our data demonstrate that nuclear YB-1 localization is associated with LRP and EGFR expression in NSCLC, and nuclear YB-1 localization and LRP and EGFR expression are of prognostic significance in NSCLC.