Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Mar;13(3):1819-1825.
doi: 10.3892/ol.2017.5637. Epub 2017 Jan 25.

Overexpression of heat-shock factor 1 is associated with a poor prognosis in esophageal squamous cell carcinoma

Yukiko Tsukao  1 , Makoto Yamasaki  1 , Yasuhiro Miyazaki  1 , Tomoki Makino  1 , Tsuyoshi Takahashi  1 , Yukinori Kurokawa  1 , Hiroshi Miyata  1 , Kiyokazu Nakajima  1 , Shuji Takiguchi  1 , Koshi Mimori  2 , Masaki Mori  1 , Yuichiro Doki  1
Affiliations

Overexpression of heat-shock factor 1 is associated with a poor prognosis in esophageal squamous cell carcinoma

Yukiko Tsukao et al. Oncol Lett. 2017 Mar.

Abstract

Heat-shock factor 1 (HSF1) is the primary regulator of the response to various stressors. A previous study showed that HSF1 expression is associated with a poor prognosis in breast cancer and hepatocellular carcinoma; however, the prognostic significance of HSF1 in esophageal squamous cell carcinoma (ESCC) is unknown. Therefore, the present study investigated the association between HSF1 expression and the clinicopathological parameters of patients, as well as the association between HSF1 expression, and heat shock protein (Hsp)27, Hsp70 and Hsp90 expression induced by HSF1, by cDNA microarray and immunohistochemistry analyses. HSF1 protein and mRNA expression were assessed in resected specimens from 270 patients with ESCC in two independent cohorts. Hsp27, Hsp70 and Hsp90 expression were also assessed in 55/270 patients. Patients with high HSF1 expression had a significantly worse OS than those with low HSF1 expression in both cohorts. In multivariate analyses, pathological T stage [hazard ratio (HR), 2.21; 95% confidence interval (CI), 1.38-3.65; P=0.0008], pathological N stage (HR, 1.73; 95% CI, 1.04-3.02; P=0.03) and HSF1 expression (HR, 2.29; 95% CI, 1.48-3.64; P=0.0002) were statistically significant independent prognostic factors. Furthermore, Hsp27 and Hsp90 expression were significantly correlated with HSF1 expression (P<0.0001), but Hsp70 expression was not (P=0.38). These results indicate that HSF1 is a prognostic factor for patients with ESCC, and that Hsp27 and Hsp90, but not Hsp70, may be the downstream targets of HSF1 in ESCC.

Keywords: esophageal squamous cell carcinoma; heat-shock factor 1; prognosis.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Kaplan-Meier overall survival curves based on the heat-shock factor 1 mRNA expression status of patients with esophageal squamous cell carcinoma in cohort 1.
Figure 2.
Figure 2.
Immunohistochemical staining showing the expression of heat-shock factor 1 (HSF1) in esophageal squamous cell carcinoma (ESCC) tumor samples from cohort 2. Representative images of (A) high HSF1 expression in ESCC, showing staining predominantly in the nuclei of tumor cells (magnification, ×200); (B) low HSF1 expression ESCC, showing almost no appreciable staining of the tumor cells (magnification, ×200); and (C) normal squamous epithelium, which is negative for HSF1 expression except for a few basal cells (magnification, ×100).
Figure 3.
Figure 3.
Kaplan-Meier overall survival curves based on the heat-shock factor 1 protein expression status of esophageal squamous cell carcinoma patients in cohort 2.
Figure 4.
Figure 4.
Overall survival curves based on (A) heat-shock protein 27 (Hsp27), (B) Hsp90 and (C) Hsp70 expression status of patients with esophageal squamous cell carcinoma.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–249. doi: 10.3322/caac.20006. - DOI - PubMed
    1. Fujita H. The history of lymphadenectomy for esophageal cancer and the future prospects for esophageal cancer surgery. Surg Today. 2015;45:140–149. doi: 10.1007/s00595-014-0841-4. - DOI - PubMed
    1. Sobin LH, Gospodarowicz MK, Wittekind Ch, editors. TNM Classification of Malignant Tumors. 7th. Wiley-Blackwell; Oxford: 2009. Oesophagus including oesophagogastric junction; pp. 65–72.
    1. Sorger PK. Heat shock factor and the heat shock response. Cell. 1991;65:363–366. doi: 10.1016/0092-8674(91)90452-5. - DOI - PubMed
    1. Qian SB, McDonough H, Boellmann F, Cyr DM, Patterson C. CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70. Nature. 2006;440:551–555. doi: 10.1038/nature04600. - DOI - PMC - PubMed