The expressions of bHLH gene HES1 and HES5 in advanced ovarian serous adenocarcinomas and their prognostic significance: a retrospective clinical study

Abstract

PurposeNotch signaling was recently found to be associated with prognosis of some cancers. The aim of the study is to investigate significance of the expression of HES1/HES5 protein, downstream effectors of Notch, in prognosis of the patients with advanced ovarian epithelial cancers.MethodsFormalin-fixed, paraffin embedded tissues and clinic-pathological parameters from 61 patients with FIGO stage IIIc–IV ovarian serous adenocarcinoma were collected, the expression of HES1 and HES5 protein were immunohistochemically detected, and the association of HES1 and HES5 expression with survival of the patients were analyzed.ResultsThe expressions of both HES1 and HES5 in adenocarcinoma were significantly higher than those in adenoma and normal control (χ2 = 32.915, P = 0.000 and χ2 = 46.863, P = 0.000 respectively). Overall survival and disease-free period were longer in HES1 low-expression patients (median 43.0 and 22.0 months) than those in high-expression patients (median 24.0 and 14.5 months). Of those, Overall survival period of patients with HES1 low-expression was significantly longer than that of those with high-expression (χ2 = 4.049, P = 0.044). Univariate analysis and multivariate Cox regression model did not show that HES1 or HES5 expression was a factor associated with survival of advanced ovarian serous adenocarcinoma patients.ConclusionsThe expressions of bHLH gene HES1 and HES5 are increased in advanced ovarian serous adenocarcinomas, and HES1 high-expression probably is a potential poor prognostic factor for the patients.

Expression Dynamics and Functions of Hes Factors in Development and Diseases

“…High and sustained expression of Hes1 protects fibroblasts against senescence or differentiation, but the expression of dominant negative-type Hes1 mutants allows quiescent fibroblasts to undergo differentiation. Increased expression of Hes1 has been reported in malignant tumors, including ovarian carcinomas and breast cancers (Wang et al, 2010;Sang, et al, 2010), but the patterns of its expression in these cells remains unknown. It is important to understand the more detailed relationships between Hes1 expression patterns or levels and cell proliferation or quiescent state.…”

Tigecycline Inhibits Glioma Growth by Regulating miRNA-199b-5p–HES1–AKT Pathway

“…Overexpression of HES1 is associated with a variety of human cancers, including T-cell acute lymphoblastic leukemia (ALL) and breast, cervical, prostate, ovarian, colon, and non-small cell lung cancer (NSCLC; refs. [21][22][23][24][25]. Recently, HES1 was shown as a self-renewal marker in cancer cells, and it enhanced the tumor-initiating capacity of tumor cells in nude mice (25).…”

Aberrant regulation of FBW7 in cancer

“…Over-expression of Notch receptors and ligands, and their target genes has been found in a variety of human cancers [133-136]. For example, the expression of Hes-1 and Hes-5 are up-regulated in advanced ovarian serous adenocarcinomas [137]. Notably, Hes-1 high expression could be a potential poor prognostic factor for ovarian cancer patients [137].…”