SERUM ANTIBODIES AGAINST GroEL AS AN ADDITIONAL RISK BIOMARKER OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMYSERUM ANTIBODIES AGAINST GroEL AS AN ADDITIONAL RISK BIOMARKER OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-2.17827Keywords:
biochemical recurrence, GroEL, heat shock protein 60, prostate cancer, radical prostatectomyAbstract
Background: The level of heat shock protein 60 (Hsp60) is elevated in tumor cells compared with normal prostate epithelium. Hsp60 is involved in tumor growth, invasion, and metastasis and is considered as a biomarker for cancer diagnosis and prognosis. Aim: To study the level of antibodies against prokaryotic homolog of human Hsp60 (GroEL) in prostate cancer (PCa) patients as an additional risk marker for the prediction of biochemical recurrence after radical prostatectomy (RP). Patients and Methods: A total of 55 patients with localized and locally advanced PCa, who had undergone RP between July 2013 and May 2014 were enrolled. Level of antibodies to GroEL and human Hsp60 was determined by enzyme-linked immunosorbent assay before surgery. Serum samples of blood donors with low reactivity to GroEL and human Hsp60 were used as controls. The relationship between IgG antibodies against bacterial Hsp60 and human Hsp60 and clinicopathological features were analyzed. The biochemical recurrence (BCR) free survival rate was estimated by the Kaplan — Meier method. The univariate and multivariate Cox regression models were used to evaluate the risk factors of BCR-free survival rate. Results: There were significant differences in anti-GroEL IgG levels between control and PCa patients while no significant differences in anti-human Hsp60 IgG levels between control and PCa patients were detected. During the follow-up period, 40/55 (72.7%) patients developed BCR. The time from surgery to BCR was from 18 to 72 months. Elevated IgG antibodies against bacterial Hsp60 in patients who had undergone RP were associated with early occurrence of biochemical relapse and lower 5-year BCR-free survival rate respectively (p < 0.001). The multivariate analysis indicated that IgG to GroEL (hazard ratio = 2.465; 95% confidence interval: 1.311–4.634, p < 0.05) could be independent prognostic factor in the patients who had developed BCR. Conclusion: Elevated levels of IgG antibodies against GroEL before surgery can predict early occurrence of BCR after RP and can serve as an additional independent risk biomarker of a BCR after RP.
References
Ferlay J, Colombet M, Soerjomataram I, Mathers C. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer 2019; 144: 1941–53. https://doi.org/10.1002/ijc.31937
Barron N, Keenan J, Gammel P, et al. Biochemical relapse following radical prostatectomy and miR-200a levels in prostate cancer. Prostate 2012; 72: 1193–9. https://doi.org/10.1002/pros.22469
Cappello F, de Macario EC, Zummo G, Macario AJ. Immunohistochemistry of human Hsp60 in health and disease: from autoimmunity to cancer. Methods Mol Biol 2011; 787: 245–54. https://doi.org/10.1007/978-1-4939-7477-1_21
Cappello F, Angilery F, de Macario EC, Macario AJ. Chaperonopathies and chaperonotherapy. Hsp60 as therapeutic target in cancer: potential benefits and risks. Curr Pharm Des 2013; 19: 452–7. https://doi.org/10.1517/14728222.2014.856417
Shi L, Chevolot Y, Souteyrand E, Laurenceau E. Autoantibodies against heat shock proteins as biomarkers for the diagnosis and prognosis of cancer. Cancer Biomark 2017; 18: 105–16. https://doi.org/10.3233/cbm-160117
Saibil H. Chaperone machines for protein folding, unfolding and disaggregation. Nat Rev Mol Cell Biol 2013; 14: 630–42. https://doi.org/10.1038/nrm3658
Handley HH, Yu J, Yu DT, et al. Autoantibodies to human heat shock protein (hsp) 60 may be induced by Escherichia coli groEL. Clin Exp Immunol 1996; 103: 429–35 https://doi.org/10.1111/j.1365-2249.1996.tb08298.x
Kimura E, Enns R, Alcaraz J, et al. Correlation of the survival of ovarian cancer patients with mRNA expression of the 60-kD heat-shock protein HSP-60. J Clin Oncol 1993; 11: 891–8. https://doi.org/10.1200/JCO.1993.11.5.891
Schneider J, Jimenez E, Marenbach K, et al. Immunohistochemical detection of HSP60-expression in human ovarian cancer. Correlation with survival in a series of 247 patients. Anticancer Res 1999; 9: 2141–6.
Chant I, Rose P, Morris A. Analysis of heat shock protein expression in myeloid leukemia cells by flow cytometry. Br J Haematol 1995; 90: 163–8. https://doi.org/10.1111/j.1365-2141.1995.tb03395.x
Kamishima T, Fukuda T, Usuda H, et al. Carcinosarcoma of the urinary bladder: expression of epithelial markers and different expression of heat shock proteins between epithelial and sarcomatous elements. Pathol Int 1997; 47: 166–73. https://doi.org/10.1111/j.1440-1827.1997.tb03735.x
Lebret T, Watson R, Molinie V, et al. Heat shock proteins HSP27, HSP60, HSP70, and HSP90: expression in bladder carcinoma. Cancer 2008; 98: 970–7. https://doi.org/10.1002/cncr.11594
Franzen B, Linder S, Alaiya A, et al. Analysis of polypeptide expression in benign and malignant human breast lesions. Electrophoresis 1997; 18: 582–7. https://doi.org/10.1002/elps.1150180341
Desmetz C, Bibeau F, Boissiere F, et al. Proteomics-based identification of HSP60 as a tumor-associated antigen in early stage breast cancer and ductal carcinoma in situ. J Proteome Res 2008; 7: 3830–7. https://doi.org/10.1021/pr800130d
Hsu P, Hsu S. Abundance of heat shock proteins (Hsp89, Hsp60, and Hsp27) in malignant cells of Hodgkin’s disease. Cancer Res 1998; 58: 5507–13.
Piselli P, Vendetti S, Vismara D, et al. Different expression of CD44, ICAM-1, and HSP60 on primary tumor and metastases of a human pancreatic carcinoma growing in SCID mice. Anticancer Res. 2000; 20: 825–31.
Trieb K, Gerth R, Windhager R, et al. Serum antibodies against the Heat shock protein 60 are elevated in patients with osteosarcoma. Immunology 2000; 201: 368–76. https://doi.org/10.1016/S0171-2985(00)80091-1
Kato S, Kato M, Hirano A, et al. The immunohistochemical expression of stress-response protein (spr) 60 in human brain tumours: relationship of srp 60 to the other five srps, proliferating cell nuclear antigen and p53 protein. Histol Histopathol 2001; 16: 809–20. https://doi.org/10.14670/HH-16.809
Cappello F, Bellafiore M, Palma A, et al. 60 Kda chaperonin (HSP60) is over-expressed during colorectal carcinogenesis. Eur J Histochem 2003; 47: 105–10. https://doi.org/10.4081/814
He Y, Wu Y, Mou Z, et al. Proteomics-based identification of HSP60 as a tumor-associated antigen in colorectal cancer. Proteomics Clin Appl 2007; 1: 336–42. https://doi.org/10.1002/prca.200600718
Castilla C, Congregado B, Conde JM, et al. Immunohistochemical expression of Hsp60 correlates with tumor progression and hormone resistance in prostate cancer. Urology 2010; 76: 1017.e1–6. https://doi.org/10.1016/j.urology.2010.05.045
Glaessgen A, Jonmarker S, Lindberg A, Nilsson D. Heat shock proteins 27, 60 and 70 as prognostic markers of prostate cancer. APMIS 2008; 116: 885–95. https://doi.org/10.1111/j.1600-0463.2008.01051.x
Cornford PA, Dodson AR, Parsons KF, et al. Heat shock protein expression independently predicts clinical outcome in prostate cancer. Cancer Res 2000; 60: 7099–105.
Cappello F, Rappa F, David S, et al. Immunohistochemical evaluation of PCNA, p53, HSP60, HSP10 and MUC-2 presence and expression in prostate carcinogenesis. Anticancer Res 2003; 23: 1325–31.
Cappello F, Bellafiore M, Palma A, et al. Expression of 60-kD heat shock protein increases during carcinogenesis in the uterine exocervix. Pathobiology 2002; 70: 83–8. https://doi.org/10.1159/000067304
Pignatelli D, Ferreira J, Soares P, et al. Immunohistochemical study of heat shock proteins 27, 60 and 70 in the normal human adrenal and in adrenal tumors with suppressed ACTH production. Microsc Res Tech 2003; 81: 15–23. https://doi.org/10.1002/jemt.10341
Vigontina O, Efimenko O, Yakovenko L, et al. Chaperon Hsp60 as autoantigen in development of dyshormonal diseases. Exp Oncol 2002; 24: 112–5.
Hamrita B, Chahed K, Kabbage M, et al. Identification of tumor antigens that elicit a humoral immune response in breast cancer patients’ sera by serological proteome analysis (SERPA). Clin Chim Acta 2008; 393: 95–102. https://doi.org/10.1016/j.cca.2008.03.017
Bodzek P, Partyka R, Damasiewicz-Bodzek A. Antibodies against Hsp60 and Hsp65 in the sera of women with ovarian cancer. J Ovarian Res 2014; 7: 30. https://doi.org/10.1186/1757-2215-7-30
Wu C, Chang Y, Chang K, et al. Salivary auto-antibodies as noninvasive diagnostic markers of oral cavity squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2014; 23: 1569–78. https://doi.org/10.1158/1055-9965.EPI-13-1269
Ma T, Schreiber C, Knutson G, et al. Effects of oxygen on the antigenic landscape of prostate cancer cells. BMC Res Notes 2015; 8: 687–93. https://doi.org/10.1186/s13104-015-1633-7
Kumar S, O’Malley J, Chaudhary AK, et al. Hsp60 and IL-8 axis promotes apoptosis resistance in cancer. Br J Cancer 2019; 121: 934–43. https://doi.org/10.1038/s41416-019-0617-0
Capello F, Czarnecka AM, La Rocca G, et al. Hsp60 and Hsp10 as antitumor molecular agents. Cancer Biol Ther 2007; 6: 487–9. https://doi.org/10.4161/cbt.6.4.4087
Grygorenko V, Yakovenko L, Vikarchuk M, et al. Antibodies against prokaryotic Hsp60 and human Hsp60 in the serum of patients with prostate cancer. Eur Urol Suppl 2016; 15: e1365. https://doi.org/10.1016/S1569-9056(16)30223-8
Ghosh J, Dohi T, Kang B, Altieri D. Hsp60 regulation of tumor cell apoptosis. J Biol Chem 2008; 283: 5188–94. https://doi.org/10.1074/jbc.M705904200
Tsai Y, Yang M, Huang C, et al. Interaction between HSP60 and b-catenin promotes metastasis. Carcinogenesis 2009; 30: 1049–57. https://doi.org/10.1093/carcin/bgp087
Wu T, Tanguay R. Antibodies against heat shock proteins in environmental stresses and diseases: friends or foe? Cell Stress Chaperones 2006; 11: 1–12. https://doi.org/10.1379/csc-155r.1
Varbio S, Biro A, Cervenak J, et al. Human anti-60 kD heat shock protein autoantibodies are characterized by basic features of natural autoantibodies. Acta Physiol Hung 2010; 97: 1–10. https://doi.org/10.1556/APhysiol.97.2010.1.1
Hrbacek J, Urban M, Hamsikova E, et al. Thirty years of research on infection of prostate cancer: No conclusive evidence for a link. A systematic review. Urol Oncol 2013; 31: 951–65. https://doi.org/10.1016/j.urolonc.2012.01.013
Cappello F, Bellafiore M, Palma A, et al. Expression of 60-kD heat shock protein increases during carcinogenesis in the uterine exocervix. Pathology 2002; 70: 83–8. https://doi.org/10.1159/000067304
Kapustian L, Kyyamova R, Gryshkova V, et al. Obtaining recombinant chaperon GroEL and its immunological cross-reactivity with Hsp60. Biopolym Cell 2009; 22: 117–20. https://doi.org/10.7124/bc.000724
Chandra D, Choy G, Tang D. Cytosolic accumulation of HSP60 during apoptosis with or without apparent mitochondrial release: evidence that its proapoptic or pro-survival functions involve differential interactions with caspase-3. J Biol Chem 2007; 282: 31289–301. https://doi.org/10.1074/jbc.M702777200
Cappello F, Macario E, Di Felice V, et al. Chlamydia trachomatis infection and anti-Hsp60 immunity: the two sides of the coin. Plos Pathogens 2009; 5: 1–9. https://doi.org/10.1371/journal.ppat.1000552
Caini S, Gandini S, Dubas M, et al. Sexually transmitted infections and prostate cancer risk: a systematic review and meta-analysis. Cancer Epidemiol 2014; 38: 329–38. https://doi.org/10.1016/j.canep.2014.06.002.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Experimental Oncology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
