Abstract
Ovarian cancer is the major gynaecologic malignancy and the leading cause of death in gynaecological cancer. Heat shock proteins (HSPs) are highly expressed in many malignant cancers and involved in metastasis including ovarian cancer. The early detection of peritoneal metastases in epithelial ovarian cancer may be more important in clinical care. HSP27, a small heat shock protein, is correlated with peritoneal metastases in epithelial ovarian cancer tissues. In this study, we investigated whether the levels of total HSP27 were detectable in serum and whether it could be a predictive biomarker for peritoneal metastases in epithelial ovarian cancer. Serum samples from 48 patients with epithelial ovarian cancer, 35 patients with benign ovarian tumours and 24 healthy women were included in this study. The serum levels of total HSP27 were measured by enzyme-linked immunosorbent assay (ELISA). There was no difference in the serum levels of total HSP27 between women with benign ovarian tumours and healthy women. However, the serum levels of total HSP27 were significantly increased in patients with epithelial ovarian cancer. The increased serum levels of total HSP27 were only seen in patients with peritoneal metastases. Furthermore, increased serum levels of total HSP27 were significantly reduced after the combination chemotherapies in patients with peritoneal metastases. These data suggest that circulating HSP27 levels were increased in epithelial ovarian cancer and correlated with peritoneal metastases. The measurement of serum HSP27 levels may be used as a potential additional indicator for peritoneal metastases in epithelial ovarian cancer and response to treatment.
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Edwards BK, Brown ML, Wingo PA, Howe HL, Ward E, Ries LAG, et al. Annual report to the nation on the status of cancer, 1975–2002, featuring population-based trends in cancer treatment. J Natl Cancer Inst. 2005;97:1407.
Agarwal R, Kaye SB. Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 2003;3:502–16.
McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. Obstet Gynecol Surv. 1996;51:288.
Nossov V, Amneus M, Su F, Lang J, Janco JM, Reddy ST, et al. The early detection of ovarian cancer: from traditional methods to proteomics. Can we really do better than serum CA-125? Am J Obstet Gynecol. 2008;199:215–23.
Chow SN, Chen RJ, Chen CH, Chang TC, Chen LC, Lee WJ, et al. Analysis of protein profiles in human epithelial ovarian cancer tissues by proteomic technology. Eur J Gynaecol Oncol. 2010;31:55–62.
Cohen M, Dromard M, Petignat P. Heat shock proteins in ovarian cancer: a potential target for therapy. Gynecol Oncol. 2010;119:164–6.
Kiang JG, Tsokos GC. Heat shock protein 70 kDa: molecular biology, biochemistry, and physiology. Pharmacol Ther. 1998;80:183–201.
Lelj-Garolla B, Mauk AG. Self-association and chaperone activity of Hsp27 are thermally activated. J Biol Chem. 2006;281:8169–74.
Jedlicka P, Mortin MA, Wu C. Multiple functions of Drosophila heat shock transcription factor in vivo. EMBO J. 1997;16:2452–62.
Khalil AA, Kabapy NF, Deraz SF, Smith C. Heat shock proteins in oncology: diagnostic biomarkers or therapeutic targets? Biochim Biophys Acta. 1816;2011:89–104.
Zoubeidi A, Gleave M. Small heat shock proteins in cancer therapy and prognosis. Int J Biochem Cell Biol. 2012;44:1646–56.
Arts HJG, Hollema H, Lemstra W, Willemse PHB, De Vries EGE, Kampinga HH, et al. Heat shock protein 27 (HSP27) expression in ovarian carcinoma: relation in response to chemotherapy and prognosis. Int J Cancer. 1999;84:234–8.
Rocchi P, So A, Kojima S, Signaevsky M, Beraldi E, Fazli L, et al. Heat shock protein 27 increases after androgen ablation and plays a cytoprotective role in hormone-refractory prostate cancer. Cancer Res. 2004;64:6595–602.
Calderwood SK, Khaleque MA, Sawyer DB, Ciocca DR. Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci. 2006;31:164–72.
Hayashi N, Peacock JW, Beraldi E, Zoubeidi A, Gleave ME, Ong CJ. Hsp27 silencing coordinately inhibits proliferation and promotes Fas-induced apoptosis by regulating the PEA-15 molecular switch. Cell Death Differ. 2012;19:990–1002.
Love S, King R. A 27 kDa heat shock protein that has anomalous prognostic powers in early and advanced breast cancer. Br J Cancer. 1994;69:743.
Zhao M, Shen F, Yin YX, Yang YY, Xiang DJ, Chen Q. Increased expression of heat shock protein 27 correlates with peritoneal metastasis in epithelial ovarian cancer. Reprod Sci. 2012;19:748–53.
Foster C, Dodson A, Ambroisine L, Fisher G, Møller H, Clark J, et al. Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement. Br J Cancer. 2009;101:1137–44.
Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 2005;10:86.
Langdon SP, Rabiasz GJ, Hirst GL, King R, Hawkins RA, Smyth JF, et al. Expression of the heat shock protein HSP27 in human ovarian cancer. Clin Cancer Res. 1995;1:1603.
Korneeva I, Bongiovanni AM, Girotra M, Caputo TA, Witkin SS. Serum antibodies to the 27-kd heat shock protein in women with gynecologic cancers. Am J Obstet Gynecol. 2000;183:18–21.
Olejek A, Damasiewicz-Bodzek A, Bodzek P, Wielkoszynski T, Zamlynski J, Stoltny P, et al. Concentrations of antibodies against heat shock protein 27 in the sera of women with ovarian carcinoma. Int J Gynecol Cancer. 2009;19:1516.
Concannon CG, Gorman AM, Samali A. On the role of Hsp27 in regulating apoptosis. Apoptosis. 2003;8:61–70.
Helm CW, States JC. Enhancing the efficacy of cisplatin in ovarian cancer treatment—could arsenic have a role. J Ovarian Res. 2009;2:2.
Kim JH, Jeong SJ, Kim B, Yun SM, Choi do Y, Kim SH. Melatonin synergistically enhances cisplatin-induced apoptosis via the dephosphorylation of ERK/p90 ribosomal S6 kinase/heat shock protein 27 in SK-OV-3 cells. J Pineal Res. 2012;52:244–52.
Karaca B, Atmaca H, Bozkurt E, Kisim A, Uzunoglu S, Karabulut B, et al. Combination of AT-101/cisplatin overcomes chemoresistance by inducing apoptosis and modulating epigenetics in human ovarian cancer cells. Mol Biol Rep. 2013;40:3925–33.
Baylot V, Andrieu C, Katsogiannou M, Taieb D, Garcia S, Giusiano S, et al. OGX-427 inhibits tumor progression and enhances gemcitabine chemotherapy in pancreatic cancer. Cell Death Dis. 2011;2:e221.
Shiota M, Bishop JL, Nip KM, Zardan A, Takeuchi A, Cordonnier T, et al. Hsp27 regulates epithelial mesenchymal transition, metastasis, and circulating tumor cells in prostate cancer. Cancer Res. 2013;73:3109–19.
Annunziata CM, Kleinberg L, Davidson B, Berner A, Gius D, Tchabo N, et al. BAG-4/SODD and associated antiapoptotic proteins are linked to aggressiveness of epithelial ovarian cancer. Clin Cancer Res. 2007;13:6585.
Adams DJ, Hajj H, Edwards DP, Bjercke RJ, McGuire WL. Detection of a Mr 24,000 estrogen-regulated protein in human breast cancer by monoclonal antibodies. Cancer Res. 1983;43:4297.
Tenniswood MP, Guenette RS, Lakins J, Mooibroek M, Wong P, Welsh JE. Active cell death in hormone-dependent tissues. Cancer Metastasis Rev. 1992;11:197–220.
Vasconsuelo A, Milanesi L, Boland R. Participation of HSP27 in the antiapoptotic action of 17beta-estradiol in skeletal muscle cells. Cell Stress Chaperones. 2010;15:183–92.
Cunat S, Hoffmann P, Pujol P. Estrogens and epithelial ovarian cancer. Gynecol Oncol. 2004;94:25–32.
Kommoss F, Pfisterer J, Thome M, Schafer W, Sauerbrei W, Pfleiderer A. Steroid receptors in ovarian carcinoma: immunohistochemical determination may lead to new aspects. Gynecol Oncol. 1992;47:317–22.
Spillman MA, Manning NG, Dye WW, Sartorius CA, Post MD, Harrell JC, et al. Tissue-specific pathways for estrogen regulation of ovarian cancer growth and metastasis. Cancer Res. 2010;70:8927–36.
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This study was supported by the Chinese National Nature Sciences Foundation (grant numbers 81100437 to M Zhao and 81072130 to JX Ding). Authors would also like to thank all the patients who donated their blood for this study.
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Zhao M and Ding JX equally contributed to this work.
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Zhao, M., Ding, J.X., Zeng, K. et al. Heat shock protein 27: a potential biomarker of peritoneal metastasis in epithelial ovarian cancer?. Tumor Biol. 35, 1051–1056 (2014). https://doi.org/10.1007/s13277-013-1139-7
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DOI: https://doi.org/10.1007/s13277-013-1139-7