Role of HSF1 expression for tumor microenvironment in intrahepatic cholangiocarcinoma.

Abstract

249 Background: Heat shock factor 1 (HSF1) is a master regulator of heat shock response. HSF1 is recently identified to play a multifaceted role in cancer progression. However, the clinical significance and biological effect of HSF1 in intrahepatic cholangiocarcinoma (IHCC) remain unknown. The aim of this study was to investigate the relationship between HSF1 expression and clinicopathological factors in IHCC patients after hepatic resection, and its possible mechanism for malignant behavior. Methods: Forty-nine patients with IHCC who undergo hepatic resection were enrolled in this study. HSF1 expressions in tumor tissue were determined by immunohistochemistry. Patients were divided into two groups, the HSF1 high and low expression group. Clinicopathological factors including prognosis were compared between the high group (n = 20) and low expression groups (n = 29) in tumor tissues. Furthermore, the correlation between HSF1 with Fbxw7 or Ki-67 expressions was also examined. Results: HSF1 expression in tumor tissues was significantly higher than that in normal tissues. HSF1 expression was not significantly correlated with any clinicopathological characteristics, including age, sex, tumor markers, maximum tumor size, tumor number, and tumor staging curability . The overall survival rate in the HSF1 high expression group was significantly worse than that in the HSF1 low expression group ( p= 0.018). On multivariate analysis, HSF1 high expression was detected as the independent prognostic factor. There was a significant inverse correlation between HSF1 and Fbxw7 expression ( p= 0.008). Ki67 labeling index was significantly higher in the high than in the low HSF1 expression group ( p= 0.030). Conclusions: HSF1 high expression in tumor tissues may be prognostic biomarker in IHCC. Targeting the Fbxw7/HSF1 axis might be a critical therapeutic strategy in IHCC.