Abstract
Levels of serum heat shock protein 27 (sHsp27) have been studied in numerous cancer types, but their potential relevance in patients with hepatocellular carcinoma (HCC) is undetermined. Our aim was to compare sHsp27 levels in patients with HCC and HCC-free controls. Specifically, we recruited 71 patients with HCC (80 % with early tumour), 80 patients with chronic liver disease (59 with liver cirrhosis and 21 with chronic active hepatitis) and 42 healthy subjects. sHsp27 was measured by immunoenzymatic assay. Results showed that sHsp27 levels were significantly (p < 0.001) higher in patients with HCC than in the other groups, particularly in those with hepatitis C virus (HCV)-related disease. In HCC patients, sHsp27 levels were not associated with prognostic risk factors, such as size/multiplicity of nodules and stage. In logistic regression analysis, performed in patients with liver disease, log-sHsp27 was associated with a significant age-adjusted 2.5-fold increased odds ratio of HCC and with a significant 4.4-fold higher odds ratio of HCC in the subgroup with HCV-related liver disease. In receiver operating characteristic curve analysis, sensitivity and specificity of the best sHsp27 cut-off value (456.5 pg/ml) for differentiating patients with HCC from those with HCC-free chronic liver disease were 70 and 73 %, respectively. In conclusion, sHsp27 levels are enhanced in patients with HCC and may represent a candidate biomarker of HCC.
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References
American Liver Tumor Study Group (1998) A randomized prospective multi-institutional trial of orthotopic liver transplantation or partial hepatic resection with or without adjuvant chemotherapy for hepatocellular carcinoma. Investigators Booklet and Protocol. United Network for Organ Sharing. Policy 3.6.4.4
Banerjee S, Lin CF, Skinner KA et al (2011) Heat shock protein 27 differentiates tolerogenic macrophages that may support human breast cancer progression. Cancer Res 71:318–327
Bruix J, Sherman M (2005) Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology 42:1208–1236
Calderwood SK, Khaleque MA, Sawyer DB et al (2006) Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci 31:164–172
Choi YW, Tan YJ, Lim SG et al (2004) Proteomic approach identifies HSP27 as an interacting partner of the hepatitis C virus NS5A protein. Biochem Biophys Res Commun 318:514–519
Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86–103
De AK, Roach SE (2004) Detection of the soluble heat shock protein 27 (hsp27) in human serum by an ELISA. J Immunoass Immunochem 25:159–170
Delhaye M, Gulbis B, Galand P et al (1992) Expression of 27-kD heat-shock protein isoforms in human neoplastic and nonneoplastic liver tissues. Hepatology 16:382–389
El-Serag HB (2004) Hepatocellular carcinoma: recent trends in the United States. Gastroenterology 127:S27–S34
El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557–2576
El-Serag HB, Mason AC, Key C (2001) Trends in survival of patients with hepatocellular carcinoma between 1977 and 1996 in the United States. Hepatology 33:62–65
Fanelli MA, Cuello Carrión FD, Dekker J et al (1998) Serological detection of heat shock protein hsp27 in normal and breast cancer patients. Cancer Epidemiol Biomark Prev 7:791–795
Gruden G, Bruno G, Chaturvedi N et al (2008) Serum heat shock protein 27 and diabetes complications in the EURODIAB prospective complications study: a novel circulating marker for diabetic neuropathy. Diabetes 57:1966–1970
Howe HL, Wingo PA, Thun MJ et al (2001) Annual report to the nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. J Natl Cancer Inst 93:824–842
Huang Q, Ye J, Huang Q et al (2010) Heat shock protein 27 is over-expressed in tumor tissues and increased in sera of patients with gastric adenocarcinoma. Clin Chem Lab Med 48:263–269
King KL, Li AF, Chau GY et al (2000) Prognostic significance of heat shock protein-27 expression in hepatocellular carcinoma and its relation to histologic grading and survival. Cancer 88:2464–2470
Lim SO, Park SG, Yoo JH et al (2005) Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules. World J Gastroenterol 11:2072–2079
Luk JM, Lam CT, Siu AF et al (2006) Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat-shock proteins (Hsp27, Hsp70, GRP78) up-regulation and their associated prognostic values. Proteomics 6:1049–1057
Mairesse N, Delhaye M, Galand P (1990) Enhanced expression of a 27 kD protein during diethylnitrosamine-induced hepatocarcinogenesis in rats. Biochem Biophys Res Commun 170:908–914
Melle C, Ernst G, Escher N et al (2007) Protein profiling of microdissected pancreas carcinoma and identification of HSP27 as a potential serum marker. Clin Chem 53:629–635
van Eden W, van der Zee R, Prakken B (2005) Heat-shock proteins induce T-cell regulation of chronic inflammation. Nat Rev Immunol 5:318–530
Vidyasagar A, Wilson NA, Djamali A (2012) Heat shock protein 27 (HSP27): biomarker of disease and therapeutic target. Fibrogenesis Tissue Repair 5:7
Welsh MJ, Gaestel M (1998) Small heat-shock protein family: function in health and disease. Ann N Y Acad Sci 851:28–35
Zimmermann M, Nickl S, Lambers C et al (2012) Discrimination of clinical stages in non-small cell lung cancer patients by serum HSP27 and HSP70: a multi-institutional case-control study. Clin Chim Acta 413:1115–1120
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This study received grant supports from Piedmont Region “Applied Scientific Research” CIPE and University of Turin.
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Gruden, G., Carucci, P., Lolli, V. et al. Serum heat shock protein 27 levels in patients with hepatocellular carcinoma. Cell Stress and Chaperones 18, 235–241 (2013). https://doi.org/10.1007/s12192-012-0377-8
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DOI: https://doi.org/10.1007/s12192-012-0377-8