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Research paper
Published online: 2021-04-20
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Are IgG antibodies to heat shock proteins HSP27 and HSP60 useful markers in endometrial cancer and cervical cancer?

Piotr Bodzek1, Bogdan Szymala2, Aleksandra Damasiewicz-Bodzek3, Iwona Janosz2, Lukasz Witek3, Anita Olejek2
DOI: 10.5603/GP.a2021.0060
·
Pubmed: 33914318
Affiliations
  1. Department of Gynaecology, Obstetrics and Oncological Gynaecology, Faculty of Medical Sciences in Zabrze Medical University of Silesia, Bytom, Poland
  2. Department of Gynaecology, Obstetrics and Oncological Gynaecology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Bytom, Poland
  3. Department of Chemistry, Faculty of Medicine and Division of Dentistry, Medical University of Silesia, Zabrze, Poland

open access

Ahead of Print
ORIGINAL PAPERS Gynecology
Published online: 2021-04-20

Abstract

Objectives: Heat shock proteins are overexpressed in many human malignancies. The role of heat shock proteins as a therapeutic target in cancer as well as their association with drug resistance were widely documented. The aim of this study was to evaluate the concentration of IgG class HSP27 and HSP60 antibodies in serum of patients with endometrial and cervical cancer, as well as to analyse the variability of concentrations of the examined antibodies depending on the cancer stage. Results:  In both endometrial and cervical cancer, the serum concentration of IgG anti-HSP27 antibody was significantly higher than in the healthy control group. The concentration of IgG anti-HSP60 antibody in endometrial cancer, cervical cancer and healthy control was similar. The median IgG anti-HSP27 antibody serum concentration of endometrial cancer patients was not correlated with FIGO-stage. In cervical cancer inverse correlation between concentration of this antibody and FIGO stage was observed. The median IgG anti-HSP60 antibody concentration in serum of endometrial cancer patients was lower in FIGO stage I and II compared to FIGO stage IV and in FIGO stage IA compared to FIGO stage IB. Concentrations of examined antibodies correlated positively with each other, both in the group of women with cancer and in the group of healthy women. The strongest correlations were found in the group of patients with endometrial cancer. Conclusions: Concentration of anti-HSP27 antibody could help in detection of cervical and endometrial cancer. We need to look for the cut-off point in large cohort studies. Anti-HSP27 and anti-HSP60 antibodies should be further evaluated for their potential usage as biomarkers in cervical and endometrial cancer as they shown some correlation with stage of disease.

Abstract

Objectives: Heat shock proteins are overexpressed in many human malignancies. The role of heat shock proteins as a therapeutic target in cancer as well as their association with drug resistance were widely documented. The aim of this study was to evaluate the concentration of IgG class HSP27 and HSP60 antibodies in serum of patients with endometrial and cervical cancer, as well as to analyse the variability of concentrations of the examined antibodies depending on the cancer stage. Results:  In both endometrial and cervical cancer, the serum concentration of IgG anti-HSP27 antibody was significantly higher than in the healthy control group. The concentration of IgG anti-HSP60 antibody in endometrial cancer, cervical cancer and healthy control was similar. The median IgG anti-HSP27 antibody serum concentration of endometrial cancer patients was not correlated with FIGO-stage. In cervical cancer inverse correlation between concentration of this antibody and FIGO stage was observed. The median IgG anti-HSP60 antibody concentration in serum of endometrial cancer patients was lower in FIGO stage I and II compared to FIGO stage IV and in FIGO stage IA compared to FIGO stage IB. Concentrations of examined antibodies correlated positively with each other, both in the group of women with cancer and in the group of healthy women. The strongest correlations were found in the group of patients with endometrial cancer. Conclusions: Concentration of anti-HSP27 antibody could help in detection of cervical and endometrial cancer. We need to look for the cut-off point in large cohort studies. Anti-HSP27 and anti-HSP60 antibodies should be further evaluated for their potential usage as biomarkers in cervical and endometrial cancer as they shown some correlation with stage of disease.

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Keywords

endometrial cancer, cervical cancer, heat shock proteins

About this article
Title

Are IgG antibodies to heat shock proteins HSP27 and HSP60 useful markers in endometrial cancer and cervical cancer?

Journal

Ginekologia Polska

Issue

Ahead of Print

Article type

Research paper

Published online

2021-04-20

DOI

10.5603/GP.a2021.0060

Pubmed

33914318

Keywords

endometrial cancer
cervical cancer
heat shock proteins

Authors

Piotr Bodzek
Bogdan Szymala
Aleksandra Damasiewicz-Bodzek
Iwona Janosz
Lukasz Witek
Anita Olejek

References (45)
  1. Chen JLY, Huang YS, Huang CY, et al. Impact of adjuvant radiotherapy on the survival of women with optimally resected stage III endometrial cancer in the era of modern radiotherapy: a retrospective study. Radiat Oncol. 2020; 15(1): 72.
  2. Muzykiewicz KP, Iwanska E, Janeczek M, et al. The analysis of the prognostic value of the neutrophil/ lymphocyte ratio and the platelet/lymphocyte ratio among advanced endometrial cancer patients. Ginekol Pol. 2021; 92(1): 16–23.
  3. Anton C, Kleine RT, Mayerhoff E, et al. Ten years of experience with endometrial cancer treatment in a single Brazilian institution: Patient characteristics and outcomes. PLoS One. 2020; 15(3): e0229543.
  4. Amant F, Moerman P, Neven P, et al. Endometrial cancer. The Lancet. 2005; 366(9484): 491–505.
  5. Reijnen C, van der Putten LJM, Bulten J, et al. Mutational analysis of cervical cytology improves diagnosis of endometrial cancer: A prospective multicentre cohort study. Int J Cancer. 2020; 146(9): 2628–2635.
  6. Zhang J, Si J, Gan Lu, et al. Inhibition of Wnt signalling pathway by XAV939 enhances radiosensitivity in human cervical cancer HeLa cells. Artif Cells Nanomed Biotechnol. 2020; 48(1): 479–487.
  7. Chen H, Wang Xi, Jia H, et al. Bioinformatics analysis of key genes and pathways of cervical cancer. Onco Targets Ther. 2020; 13: 13275–13283.
  8. Qi YX, Liu K, Yin J, et al. Evaluation of short- and long-term efficacy of chemoradiotherapy for advanced cervical cancer using HSP70 protein combined with multimodal MRI. J Cell Biochem. 2018; 119(4): 3017–3029.
  9. de Freitas AC, Gurgel A, Chagas B, et al. Susceptibility to cervical cancer: An overview. Gynecologic Oncology. 2012; 126(2): 304–311.
  10. Tomalczyk A, Tomasik B, Moszynska-Zielinska M, et al. The assessment of spectral Doppler parameters in uterine arteries of patients with locally advanced squamous cell cervical cancer. Ginekol Pol. 2019; 90(11): 622–627.
  11. Singh IS, Hasday JD, Hasday JD, et al. Fever and the heat shock response: distinct, partially overlapping processes. Cell Stress Chaperones. 2000; 5(5): 471–480, doi: 10.1379/1466-1268(2000)005<0471:fathsr>2.0.co;2.
  12. Kim HJ, Hwang NaR, Lee KJ. Heat shock responses for understanding diseases of protein denaturation. Mol Cells. 2007; 23(2): 123–131.
  13. Horowitz M, Robinson SDM. Heat shock proteins and the heat shock response during hyperthermia and its modulation by altered physiological conditions. Prog Brain Res. 2007; 162: 433–446.
  14. Dubrez L, Causse S, Borges Bonan N, et al. Heat-shock proteins: chaperoning DNA repair. Oncogene. 2020; 39(3): 516–529.
  15. Stangl S, Tontcheva N, Sievert W, et al. Heat shock protein 70 and tumor-infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). Int J Cancer. 2018; 142(9): 1911–1925.
  16. Brünnert D, Langer C, Zimmermann L, et al. The heat shock protein 70 inhibitor VER155008 suppresses the expression of HSP27, HOP and HSP90β and the androgen receptor, induces apoptosis, and attenuates prostate cancer cell growth. J Cell Biochem. 2020; 121(1): 407–417.
  17. Rottach AM, Ahrend H, Martin B, et al. Cabazitaxel inhibits prostate cancer cell growth by inhibition of androgen receptor and heat shock protein expression. World J Urol. 2019; 37(10): 2137–2145.
  18. Hoter A, Naim HY. Heat shock proteins and ovarian cancer: important roles and therapeutic opportunities. Cancers (Basel). 2019; 11(9).
  19. Guzel E, Basar M, Ocak N, et al. Bidirectional interaction between unfolded-protein-response key protein HSPA5 and estrogen signaling in human endometrium. Biol Reprod. 2011; 85(1): 121–127.
  20. Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 2005; 10(2): 86–103.
  21. Wataba K, Saito T, Fukunaka K, et al. Over-expression of heat shock proteins in carcinogenic endometrium. Int J Cancer. 2001; 91(4): 448–456, doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1077>3.0.co;2-f.
  22. Geisler JP, Tammela JE, Manahan KJ, et al. HSP27 in patients with ovarian carcinoma: still an independent prognostic indicator at 60 months follow-up. Eur J Gynaecol Oncol. 2004; 25(2): 165–168.
  23. Heidari F, Rabizadeh S, Sadat Salehi S, et al. Serum HSP70 level in patients with endometrial cancer with and without diabetes. Gynecol Endocrinol. 2020; 36(4): 351–355.
  24. Jakubowicz-Gil J, Paduch R, Skalicka-Woźniak K, et al. Hsps responsible for apoptosis induction failure in cervical cancer cells upon osthole and tamoxifen treatment. Postępy Higieny i Medycyny Doświadczalnej. 2019; 73: 563–571.
  25. Han S, Cheng Z, Zhao X, et al. Diagnostic value of heat shock protein 90 and squamous cell carcinoma antigen in detection of cervical cancer. J Int Med Res. 2019; 47(11): 5518–5525.
  26. Hou Y, Li T, Gan W, et al. Prognostic significance of mutant-allele tumor heterogeneity in uterine corpus endometrial carcinoma. Ann Transl Med. 2020; 8(6): 339.
  27. Helpman L, Perri T, Lavee N, et al. Impact of adjuvant treatment on outcome in high-risk early-stage endometrial cancer: a retrospective three-center study. Int J Gynecol Cancer. 2019; 29(1): 133–139.
  28. van Walree IC, Hamaker ME, de Rooij BH, et al. Do age and comorbidity impair recovery during two years after treatment for endometrial cancer? J Geriatr Oncol. 2020; 11(7): 1078–1086.
  29. Ioachin E. Immunohistochemical tumour markers in endometrial carcinoma. Eur J Gynaecol Oncol. 2005; 26(4): 363–371.
  30. Ramezani A, Aghakhani A, Soleymani S, et al. Significance of serum antibodies against HPV E7, Hsp27, Hsp20 and Hp91 in Iranian HPV-exposed women. BMC Infect Dis. 2019; 19(1): 142.
  31. Boeddeker SJ, Baston-Buest DM, Altergot-Ahmad O, et al. Syndecan-1 knockdown in endometrial epithelial cells alters their apoptotic protein profile and enhances the inducibility of apoptosis. Mol Hum Reprod. 2014; 20(6): 567–578.
  32. Neuer A, Spandorfer SD, Giraldo P, et al. The role of heat shock proteins in reproduction. Hum Reprod Update. 2000; 6(2): 149–159.
  33. Garrido C, Brunet M, Didelot C, et al. Heat shock proteins 27 and 70: anti-apoptotic proteins with tumorigenic properties. Cell Cycle. 2006; 5(22): 2592–2601.
  34. Vidyasagar A, Wilson NA, Djamali A. Heat shock protein 27 (HSP27): biomarker of disease and therapeutic target. Fibrogenesis Tissue Repair. 2012; 5(1): 7.
  35. Najafi M, Goradel NH, Farhood B, et al. Tumor microenvironment: Interactions and therapy. J Cell Physiol. 2019; 234(5): 5700–5721.
  36. Nolan KD, Franco OE, Hance MW, et al. Tumor-secreted Hsp90 subverts polycomb function to drive prostate tumor growth and invasion. J Biol Chem. 2015; 290(13): 8271–8282.
  37. Lee JC, Sim DY, Lee HJ, et al. MicroRNA216b mediated downregulation of HSP27/STAT3/AKT signaling is critically involved in lambertianic acid induced apoptosis in human cervical cancers. Phytother Res. 2021; 35(2): 898–907.
  38. Seigneuric R, Mjahed H, Gobbo J, et al. Heat shock proteins as danger signals for cancer detection. Front Oncol. 2011; 1: 37.
  39. Sznurkowski J, Knapp P, Bodnar L, et al. Recommendations of the Polish Gynecological Oncology Society for the diagnosis andtreatment of endometrial cancer. Current Gynecologic Oncology. 2017; 15(1): 34–44.
  40. Colombo N, Creutzberg C, Amant F, et al. ESMO-ESGO-ESTRO Endometrial Consensus Conference Working Group. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up. Int J Gynecol Cancer. 2016; 26(1): 2–30.
  41. Ono K, Eguchi T, Sogawa C, et al. HSP-enriched properties of extracellular vesicles involve survival of metastatic oral cancer cells. J Cell Biochem. 2018; 119(9): 7350–7362.
  42. Fujiwara T, Eguchi T, Sogawa C, et al. Carcinogenic epithelial-mesenchymal transition initiated by oral cancer exosomes is inhibited by anti-EGFR antibody cetuximab. Oral Oncol. 2018; 86: 251–257.
  43. Engerud H, Tangen IL, Berg A, et al. High level of HSF1 associates with aggressive endometrial carcinoma and suggests potential for HSP90 inhibitors. Br J Cancer. 2014; 111(1): 78–84.
  44. Yu S, Cheng M, Hou L, et al. HSF1 expression in cervical carcinoma and its correlation with clinical pathological characteristics and prognosis. J Third Mil Med Univ. 2017; 36: 560–563.
  45. Zhang L, Hu Z, Zhang Y, et al. Proteomics analysis of proteins interacting with heat shock factor 1 in squamous cell carcinoma of the cervix. Oncol Lett. 2019; 18(3): 2568–2575.

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