Increased expression of heat shock factor 1 (HSF1) is associated with poor survival in gastric cancer patients

Abstract

BackgroundHeat shock factor 1 (HSF1) was initially identified as a transcription factor encoding heat shock proteins, which assist in refolding or degrading damaged proteins. Recent studies have reported that HSF1 can act as an oncogene that regulates tumour progression. The present study aimed to elucidate the clinicopathological significance and prognostic value of HSF1 expression in gastric cancer (GC).MethodsThe data from The Cancer Genome Atlas (TCGA) were used to analyse HSF1 expression in GC and normal tissues, while 8 pairs of freshly frozen tissue samples were used to investigate HSF1 expression at the mRNA and protein levels in GC tissues and adjacent normal tissues using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting assays. The correlations between HSF1 expression and clinicopathological parameters, including the survival rate, were investigated in 117 GC tissue samples by immunohistochemical analysis.ResultsThe results of bioinformatics analysis, qRT-PCR, and western blot showed that HSF1 expression was higher in GC tissues than in normal tissues. High HSF1 expression was found in 54.7% (64/117) patients. Patients with high HSF1 expression had larger tumour size (P = 0.001), advanced Bornmann classification (P = 0.002), advanced depth of invasion (P = 0.015), lymph node metastasis (P<0.001), distant metastasis (P = 0.011) and tumour-node-metastasis (P<0.001). Moreover, the Kaplan-Meier and Cox proportional hazards analyses indicated that high HSF1 expression was significantly associated with poor overall survival and recurrence-free survival in GC patients and that high HSF1 expression was an independent prognostic factor for the long-term survival in GC patients.ConclusionsTaken together, our results show that high HSF1 expression is significantly correlated with advanced tumour progression and poor prognosis. In addition, HSF1 expression can serve as a biomarker for the prognosis of patients with GC.

HSF1Base: A Comprehensive Database of HSF1 (Heat Shock Factor 1) Target Genes

“…In hepatocellular carcinoma cells, HSF1 modulates E-Cadherin expression through directly regulating Snail1 transcription [52]. Finally, in gastric cancer cells HSF1 overexpression stimulates vimentin, N -cadherin, and Snail1 expression, and decreases the level of E-cadherin [53]. Taken together, it is plausible that HSF1 regulates cadherin , teneurin, and nectin genes directly in human breast epithelium.…”

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

“…In addition, Family with sequence similarity member C (FAM3C) is a commonly known interleukin-like EMT inducer, and it has been demonstrated that the upregulation of HSF1 is the underlying mechanism of FAM3C-mediated tumorigenesis [90]. In gastric cancer, the overexpression of HSF1 has been observed in the patient samples, suggesting HSF1 to be the poor prognosis factor [91,92]. Regarding cancer cell defense mechanism, it has been shown that HSF1 forms a positive feedback loop with pyruvate dehydrogenase 3 (PDK3) to drive chemoresistance of cancers [93].…”

Natural compound rhein suppresses colorectal cancer cells growth through mTOR/p70S6 kinase pathway in vitro and in vivo

“…HSF1 is a master regulator of the heat shock response, which can promote malignant transformation, cancer cell proliferation, and survival [28]. Recent studies showed that HSF1 can act as an oncogene and be strongly related to advanced tumor progression and poor prognosis in gastric cancer [39], and breast cancer [40,41]. A previous study demonstrated that mTOR is essential for the HSF1 activation and heat shock protein synthesis [29].…”