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

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

doi:10.3892/ol.2017.5637

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

Authors:
- Yukiko Tsukao
- Makoto Yamasaki
- Yasuhiro Miyazaki
- Tomoki Makino
- Tsuyoshi Takahashi
- Yukinori Kurokawa
- Hiroshi Miyata
- Kiyokazu Nakajima
- Shuji Takiguchi
- Koshi Mimori
- Masaki Mori
- Yuichiro Doki
View Affiliations

Affiliations: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565‑0871, Japan, Department of Molecular and Cellular Biology, Division of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Ohita 874‑0838, Japan
Published online on: January 25, 2017 https://doi.org/10.3892/ol.2017.5637
Pages: 1819-1825

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar : PubMed/NCBI
2	Fujita H: The history of lymphadenectomy for esophageal cancer and the future prospects for esophageal cancer surgery. Surg Today. 45:140–149. 2015. View Article : Google Scholar : PubMed/NCBI
3	Sobin LH, Gospodarowicz MK and Wittekind Ch: Oesophagus including oesophagogastric junctionTNM Classification of Malignant Tumors. 7th. Wiley-Blackwell; Oxford: pp. 65–72. 2009
4	Sorger PK: Heat shock factor and the heat shock response. Cell. 65:363–366. 1991. View Article : Google Scholar : PubMed/NCBI
5	Qian SB, McDonough H, Boellmann F, Cyr DM and Patterson C: CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70. Nature. 440:551–555. 2006. View Article : Google Scholar : PubMed/NCBI
6	Page TJ, Sikder D, Yang L, Pluta L, Wolfinger RD, Kodadek T and Thomas RS: Genome-wide analysis of human HSF1 signaling reveals a transcriptional program linked to cellular adaptation and survival. Mol Biosyst. 2:627–639. 2006. View Article : Google Scholar : PubMed/NCBI
7	Dai C, Whitesell L, Rogers AB and Lindquist S: Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell. 130:1005–1018. 2007. View Article : Google Scholar : PubMed/NCBI
8	Li S, Ma W, Fei T, Lou Q, Zhang Y, Cui X, Qin X, Zhang J, Liu G, Dong Z, et al: Upregulation of heat shock factor 1 transcription activity is associated with hepatocellular carcinoma progression. Mol Med Rep. 10:2313–2321. 2014.PubMed/NCBI
9	Santagata S, Hu R, Lin NU, Mendillo ML, Collins LC, Hankinson SE, Schnitt SJ, Whitesell L, Tamimi RM, Lindquist S and Ince TA: High levels of nuclear heat-shock factor 1 (HSF1) are associated with poor prognosis in breast cancer. Proc Natl Acad Sci USA. 108:18378–18383. 2011. View Article : Google Scholar : PubMed/NCBI
10	Enders GH: Cyclins in breast cancer: Too much of a good thing. Breast Cancer Res. 4:145–147. 2002. View Article : Google Scholar : PubMed/NCBI
11	Quackenbush J: Microarray data normalization and transformation. Nat Genet. 32:(Suppl). S496–S501. 2002. View Article : Google Scholar
12	Brazma A, Hingamp P, Quackenbush J, Sherlock G, Spellman P, Stoeckert C, Aach J, Ansorge W, Ball CA, Causton HC, et al: Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet. 29:365–371. 2001. View Article : Google Scholar : PubMed/NCBI
13	Khalil AA, Kabapy NF, Deraz SF and Smith C: Heat shock proteins in oncology: Diagnostic biomarkers or therapeutic targets? Biochim Biophys Acta. 1816:89–104. 2011.PubMed/NCBI
14	Ciocca DR and Calderwood SK: Heat shock proteins in cancer: Diagnostic, prognostic, predictive and treatment implications. Cell Stress Chaperones. 10:86–103. 2005. View Article : Google Scholar : PubMed/NCBI
15	Kaigorodova EV and Bogatyuk MV: Heat shock proteins as prognostic markers of cancer. Curr Cancer Drug Targets. 14:713–726. 2014. View Article : Google Scholar : PubMed/NCBI
16	Ciocca DR and Vargas-Roig LM: Hsp27 as a prognostic and predictive factor in cancer. Prog Mol Subcell Biol. 28:205–218. 2002. View Article : Google Scholar : PubMed/NCBI
17	Kim KK, Jang TJ and Kim JR: HSP70 and ER expression in cervical intraepithelial neoplasia and cervical cancer. J Korean Med Sci. 13:383–388. 1998. View Article : Google Scholar : PubMed/NCBI
18	Chuma M, Sakamoto M, Yamazaki K, Ohta T, Ohki M, Asaka M and Hirohashi S: Expression profiling in multistage hepatocarcinogenesis: Identification of HSP70 as a molecular marker of early hepatocellular carcinoma. Hepatology. 37:198–207. 2003. View Article : Google Scholar : PubMed/NCBI
19	Wu C: Heat shock transcription factors: Structure and regulation. Annu Rev Cell Dev Biol. 11:441–469. 1995. View Article : Google Scholar : PubMed/NCBI
20	Calderwood SK, Xie Y, Wang X, Khaleque MA, Chou SD, Murshid A, Prince T and Zhang Y: Signal transduction pathways leading to heat shock transcription. Sign Transduct Insights. 2:13–24. 2010. View Article : Google Scholar : PubMed/NCBI
21	Khaleque MA, Bharti A, Gong J, Gray PJ, Sachdev V, Ciocca DR, Stati A, Fanelli M and Calderwood SK: Heat shock factor 1 represses estrogen-dependent transcription through association with MTA1. Oncogene. 27:1886–1893. 2008. View Article : Google Scholar : PubMed/NCBI
22	Gabai VL, Meng L, Kim G, Mills TA, Benjamin IJ and Sherman MY: Heat shock transcription factor Hsf1 is involved in tumor progression via regulation of hypoxia-inducible factor 1 and RNA-binding protein HuR. Mol Cell Biol. 32:929–940. 2012. View Article : Google Scholar : PubMed/NCBI
23	Lyu X, Huang J, Mao Y, Liu Y, Feng Q, Shao K, Gao S, Jiang Y, Wang J and He J: Adjuvant chemotherapy after esophagectomy: Is there a role in the treatment of the lymph node positive thoracic esophageal squamous cell carcinoma? J Surg Oncol. 110:864–868. 2014. View Article : Google Scholar : PubMed/NCBI
24	Ruiz MI Gallegos, Floor K, Roepman P, Rodriguez JA, Meijer GA, Mooi WJ, Jassem E, Niklinski J, Muley T, van Zandwijk N, et al: Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target. PLoS One. 3:e00017222008.PubMed/NCBI
25	Nakamura M, Iwahashi M, Nakamori M, Ojima T, Katsuda M, Iida T, Hayata K, Kato T and Yamaue H: New prognostic score for the survival of patients with esophageal squamous cell carcinoma. Surg Today. 44:875–883. 2014. View Article : Google Scholar : PubMed/NCBI
26	Pick E, Kluger Y, Giltnane JM, Moeder C, Camp RL, Rimm DL and Kluger HM: High HSP90 expression is associated with decreased survival in breast cancer. Cancer Res. 67:2932–2937. 2007. View Article : Google Scholar : PubMed/NCBI
27	Solit DB, Scher HI and Rosen N: Hsp90 as a therapeutic target in prostate cancer. Semin Oncol. 30:709–716. 2003. View Article : Google Scholar : PubMed/NCBI
28	Romani AA, Crafa P, Desenzani S, Graiani G, Lagrasta C, Sianesi M, Soliani P and Borghetti AF: The expression of HSP27 is associated with poor clinical outcome in intrahepatic cholangiocarcinoma. BMC Cancer. 7:2322007. View Article : Google Scholar : PubMed/NCBI
29	Bauer K, Nitsche U, Slotta-Huspenina J, Drecoll E, von Weyhern CH, Rosenberg R, Höfler H and Langer R: High HSP27 and HSP70 expression levels are independent adverse prognostic factors in primary resected colon cancer. Cell Oncol (Dordr). 35:197–205. 2012. View Article : Google Scholar : PubMed/NCBI
30	Smyth T, Van Looy T, Curry JE, Rodriguez-Lopez AM, Wozniak A, Zhu M, Donsky R, Morgan JG, Mayeda M, Fletcher JA, et al: The HSP90 inhibitor, AT13387, is effective against imatinib-sensitive and -resistant gastrointestinal stromal tumor models. Mot Cancer Ther. 11:1799–1808. 2012. View Article : Google Scholar
31	Wagner AJ, Agulnik M, Heinrich MC, Mahadevan D, Riedel RF, von Mehren M, Trent J, Demetri GD, Corless CL and Yule M: Dose-escalation study of a second-generation non-ansamycin HSP90 inhibitor, onalespib (AT13387), in combination with imatinib in patients with metastatic gastrointestinal stromal tumour. Eur J Cancer. 61:94–101. 2016. View Article : Google Scholar : PubMed/NCBI