Elevated of HSP90 associates with expression of EGFR levels and predicts poor prognosis in non-small cell lung cancer patients

Abstract

Abstract Background The molecular chaperone protein HSP90 is a crucial mediator of proteostasis in eukaryotic cells under various stress conditions. EGFR participates in signal transduction relating to tumorigenesis and progression. The relationship between the combined expression of HSP90 and EGFR in non-small cell lung cancer (NSCLC) and clinicopathological features and long-term prognosis is not clear. Methods We analyzed The Cancer Genome Atlas (TCGA) gene data from Xiantao platform and GEPIA2 to study the expression of HSP90 and EGFR on mRNA level and their correlation in patients with NSCLC. Besides, 53 normal lung samples and 352 paraffin-embedded NSCLC were selected randomly for immunohistochemical (IHC) staining with anti-HSP90 and anti-EGFR antibodies, respectively. Results The TCGA data revealed that HSP90 and EGFR expression on mRNA and protein was significantly higher in NSCLC patients than non-cancerous lung tissues (Non-CLT) (both p < 0.05). Moreover, increased HSP90 showed a positively correlation with EGFR in mRNA levels (both p < 0.0001). Higher HSP90 expression appeared in lymph node metastasis (LNM) or advanced clinical stage of NSCLC (p = 0.019, p = 0.013, respectively). The survival rate of high expression of HSP90 and EGFR alone or in combination was lower than that of other phenotypes in NSCLC (p < 0.001, P = 0.011, p < 0.001, respectively). In multivariate Cox proportional hazard regression analysis, HSP90 and EGFR were further identified as independent poor prognostic factors in NSCLC. Conclusions Elevated HSP90 and EGFR might suggest a synergistical role in promoting the development in patients with NSCLC. High expression of these two proteins might be novel prognostic biomarker for NSCLC, who provides potential application value for NSCLC targeted therapy.