Abstract: | Background: Heat Shock Protein 90 (Hsp90) is an ATP-dependent molecular chaperone that was required for the stability and function of more than 200 signaling proteins that promote cancer cell growth and/or survival. It exists as multiple isoforms that includes Hsp90-alpha and Hsp90-beta in the cytoplasm and GRP94 and TRAP1 localized to the ER and mitochondria, respectively. We investigated the relationship with clinical outcome and the expression of Hsp90-beta, GRP94 in the resected non-small cell lung cancer (NSCLC) patient. Methods: We obtained surgical tissue specimens from 208 patients with NSCLC (stage IA, 40; stage IB, 57; stage IIA, 22; stage IIB, 50; stage IIIA, 27; stage IIIB, 12) who underwent surgical resection of their tumors for immunohistochemical analyses of Hsp90-beta, GRP94. Clinical characteristics, survival were analyzed according to immunohistochemical expression of Hsp90-beta, GRP94 using the χ2 test, Kaplan–Meier method, and Cox proportional hazard model. Results: No correlations were observed between the expression of Hsp90-beta, GRP94 and several clincopathological factors. In a survival analysis, the expression of Hsp90-beta was significantly related to overall survival (OS, log-rank test, p=0.021). The OS was 95.97 months (95% confidence interval[CI], 48.31~143.63) with the low expression group of Hsp90-beta, as compared with 31.6 months (95% CI, 10.58~52.62) with high expression group (hazard ratio[HR], 1.95; 95% CI, 1.08~3.48). The expression of GRP94 was also significantly related to OS(log-rank test, p=0.036). The OS was 72.43 months (95% CI, 47.58~97.29) with the low expression group of GRP94, as compared with 32.27 months (95% CI, 18.48~46.06) with high expression group (HR, 1.64; 95% CI, 1.03~2.63). Conclusions: We found that the immunohistochemically high expression of Hsp90-beta, GRP94 were independent prognostic factors for reduced survival, although further large prospective studies are needed to validate our findings. |