Upregulation of Nuclear Heat Shock Factor 1 Contributes to Tumor Angiogenesis and Poor Survival in Patients With Non-Small Cell Lung Cancer.

BACKGROUND

The aim of this study was to detect the expression of heat shock factor 1 (HSF1) and microvessel density (MVD) in patients with non-small cell lung cancer (NSCLC) and to examine the relevance between HSF1 and angiogenesis, clinicopathologic factors, and prognosis.

METHODS

Immunohistochemical staining was used to examine the level of expression of HSF1 and CD34. MVD was used to detect the number of microvessels by counting CD34(+) endothelial cells. Their relationship with clinicopathologic factors and prognosis in patients with NSCLC was determined using IBM SPSS Statistics, version 19 (SPSS Inc, Chicago, IL).

RESULTS

The level of expression of HSF1 was increased significantly in NSCLC. HSF1 overexpression was observed in 45 patients and was significantly associated with MVD (p = 0.005). The overexpression of HSF1 was not associated with patient sex, age, tumor size, histologic type, or differentiation, but it was significantly associated with node metastasis (p = 0.005) and clinical stage (p = 0.006). HSF1 overexpression and high MVD were significantly associated with poor 5-year disease-free survival (p = 0.001 and p = 0.006, respectively). Patients with HSF1 overexpression and high MVD had a significantly poor overall survival (p = 0.006 and p = 0.019, respectively) and disease-specific survival (p = 0.005 and p = 0.016, respectively). Multivariate analysis showed that HSF1 overexpression was an independent prognosticator for poor overall, disease-specific, and disease-free survival (p = 0.040, p = 0.046, and p = 0.004, respectively).

CONCLUSIONS

Overexpression of HSF1 is common and significantly correlated with tumor angiogenesis in NSCLC. Patients with high HSF1 expression had poorer overall, disease-free, and disease-specific survival. These current findings suggest that HSF1 may serve as a novel prognostic marker and potential therapeutic target molecule for antiangiogenic therapy in patients with NSCLC.