Hubungan antara Ekspresi Heat Shock Protein-70 (HSP70) dengan Skor Risk of Ovarian Cancer Relapse (ROVAR) pada Pasien Kanker Ovarium Epitelial yang Dilakukan Operasi dan Dilanjutkan dengan Kemoterapi

https://doi.org/10.22146/jkr.69698

Lilik Gretta Damaianty(1*), Ardhanu Kusumanto(2), Agung Dewanto(3)

(1) UGM
(2) Departemen Obstetri dan Ginekologi, FKKMK UGM
(3) Departemen Obstetri dan Ginekologi, FKKMK UGM
(*) Corresponding Author

Abstract


Background: Ovarian cancer is one of the leading causes of death in gynecological malignancies which occupies the third place in the world.  One of largest challenge in epithelial ovarian cancer therapy is resistance to chemotherapy. Increased of  Heat Shock Protein-70 (HSP70) expression associated with the progressivity of tumor cells growth through the resistance process against chemotherapy, whereas Risk Of Ovarian Cancer Relapse (ROVAR) score is a tool that used to predict the ovarian cancer recurrence risk in patient who underwent surgery followed by chemotherapy.Objective: This study is aimed to evaluate the correlation between HSP70 expression and ROVAR score in patient with epithelial ovarian cancer who underwent first line therapy.   Method: This is a retrospective cohort study that involve 42 subjects with epithelial ovarian cancer who had been through surgery (optimal or suboptimal surgery) followed by chemotherapy.  Immunohistochemical staining of pre chemotherapy paraffin blocks was performed using HSP70 antibody and recurrence risk was calculated using ROVAR scores after surgery followed by chemotherapy. The external variables evaluated were age, parity, Body Mass Index (BMI), menopause history, and surgical type.  Data analysis used Chi Square test, spearman test, and logistic regression analysis.Result and Discussion: Of the total 42 subjects who met the inclusion criteria, most found in advanced stage with the age mean is 54,3 years old.  In the ROVAR score measurement, in high risk category is found about 32(76.19%), while in the medium risk and low risk category is 10 (23.81%). On the other hand, strong HSP70 expression was found in 36(85,71%), moderate HSP70 expression in 6(14,39%), and weak HSP70 expression was not found.  Based on Spearman's correlative test, there was a positive, very strong, and significant correlation between the expression of HSP70 and risk allocation according to ROVAR score (r=0.717, p=0.000). As well as in multivariate analysis, HSP70 expression had a statistically and clinically significant relationship with ROVAR score (p=0.017; RR 2.710; 95% CI 0.366-5.054) which strong HSP70 expression was 2.71 times more likely to have a high risk of recurrence according to ROVAR score.Conclusion: There is a positive, very strong, and significantly meaning between HSP70 expression and ROVAR score.  Increased in HSP70 expression may lead to increased recurrence risk according to ROVAR score.  Both could be used to predict recurrence in epithelial ovarian cancer post first line therapy.Keywords: Epithelial ovarian cancer, HSP70, ROVAR score, recurrence.

Keywords


Epithelial ovarian cancer; HSP70; ROVAR score; recurrence

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References

Bray, F., Ferlay, J., & Soerjomataram, I. (2018). Global Cancer Statistics 2018 : GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. 394–424. https://doi.org/10.3322/caac.21492

Duska, L. R., & Kohn, E. C. (2017). The new classifications of ovarian, fallopian tube, and primary peritoneal cancer and their clinical implications. Annals of Oncology, 28(Supplement 8), viii8–viii12.https://doi.org/10.1093/annonc/mdx445

Ushijima, K. (2010). Treatment for recurrent ovarian cancer - At first relapse. Journal of Oncology, 2010(di). https://doi.org/10.1155/2010/497429

The World Ovarian Cancer Coalition. (2018). The World Ovarian Cancer Coalition Atlas: Global Trends in Incidence, Mortality and Survival. The Every Woman Study, April, 1–39.

Bhatla, N., & Denny, L. (2018). FIGO Cancer Report 2018. 143, 2–3. https://doi.org/10.1002/ijgo.12608

Cohen, M., Dromard, M., & Petignat, P. (2010). Heat shock proteins in ovarian cancer: A potential target for therapy. Gynecologic Oncology, 119(1), 164–166.https://doi.org/10.1016/j.ygyno.2010.05.027

Albakova, Z., Armeev, G. A., Kanevskiy, L. M., Kovalenko, E. I., & Sapozhnikov, A. M. (2020). HSP70 Multi-Functionality in Cancer. Cells, 9(3), 1–26. https://doi.org/10.3390/cells9030587

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013

Li, X.-F., Hua, T., Li, Y., Tian, Y.-J., Huo, Y., & Kang, S. (2021). The HSP70 gene predicts prognosis and response to chemotherapy in epithelial ovarian cancer. Annals of Translational Medicine, 9(9), 806–806. https://doi.org/10.21037/atm-21-2087

ELPEK, G. O., KARAVELI, S., SIMSEK, T., KELES, N., & AKSOY, N. H. (2003). Expression of heat-shock proteins hsp27, hsp70 and hsp90 in malignant epithelial tumour of the ovaries. Correlation with clinicopathologic factors and survival. Apmis, 111(4), 523–530. https://doi.org/10.1034/j.1600-0463.2003.1110411.x

Dahlan SM. Langkah-langkah membuat proposal penelitian bidang kedokteran dan kesehatan. 2nd ed. Jakarta: Salemba Medika; 2009.

Momenimovahed, Z., Tiznobaik, A., Taheri, S., & Salehiniya, H. (2019). Ovarian cancer in the world: Epidemiology and risk factors. International Journal of Women’s Health, 11, 287–299. https://doi.org/10.2147/IJWH.S197604

Siegel, R. L., Miller, K. D., Fuchs, H. E., & Jemal, A. (2021). Cancer Statistics, 2021. CA: A Cancer Journal for Clinicians, 71(1), 7–33. https://doi.org/10.3322/caac.21654

Kang, H.-J., Moon, H.-S., & Chung, H.-W. (2014). The expression of FAS-associated factor 1 and heat shock protein 70 in ovarian cancer. Obstetrics & Gynecology Science, 57(4), 281. https://doi.org/10.5468/ogs.2014.57.4.281

Syam, D. M., Magister, P., Klinis, K., Obstetri, D., Ginekologi, D. A. N., Kedokteran, F., & Sumatera, U. (2018). Analisis faktor faktor yang berhubungan dengan kejadian rekurensi kanker ovarium epitel di rsup h adam malik medan tahun 2018 tesis magister.

Liu, X. X., Ye, H., Wang, P., Li, L. X., Zhang, Y., & Zhang, J. Y. (2017). Proteomic-based identification of HSP70 as a tumor-associated antigen in ovarian cancer. Oncology Reports, 37(5), 2771–2778. https://doi.org/10.3892/or.2017.5525

Pearce, C. L., Templeman, C., Rossing, M. A., Lee, A., Near, A. M., Webb, P. M., Nagle, C. M., Doherty, J. A., Cushing-Haugen, K. L., Wicklund, K. G., Chang-Claude, J., Hein, R., Lurie, G., Wilkens, L. R., Carney, M. E., Goodman, M. T., Moysich, K., Kjaer, S. K., Hogdall, E., … Berchuck, A. (2012). Association between endometriosis and risk of histological subtypes of ovarian cancer: A pooled analysis of case-control studies. The Lancet Oncology, 13(4), 385–394. https://doi.org/10.1016/S1470-2045(11)70404-1

Kim, S. J., Rosen, B., Fan, I., Ivanova, A., Mclaughlin, J. R., Risch, H., Narod, S. A., & Kotsopoulos, J. (2017). Epidemiologic factors that predict long-term survival following a diagnosis of epithelial ovarian cancer. November 2016, 964–971. https://doi.org/10.1038/bjc.2017.35

Nagle, C. M., Dixon, S. C., Jensen, A., Kjaer, S. K., Modugno, F., DeFazio, A., Fereday, S., Hung, J., Johnatty, S. E., Fasching, P. A., Beckmann, M. W., Lambrechts, D., Vergote, I., Van Nieuwenhuysen, E., Lambrechts, S., Risch, H. A., Rossing, M. A., Doherty, J. A., Wicklund, K. G., … Webb, P. M. (2015). Obesity and survival among women with ovarian cancer: Results from the Ovarian Cancer Association Consortium. British Journal of Cancer, 113(5), 817–826. https://doi.org/10.1038/bjc.2015.245

Hew, K. E., Bakhru, A., Harrison, E., Turan, M. O., MacDonald, R., Im, D. D., & Rosenshein, N. B. (2013). The Effect of Obesity on the Time to Recurrence in Ovarian Cancer: A Retrospective Study. Clinical Ovarian and Other Gynecologic Cancer, 6(1–2), 31–35. https://doi.org/10.1016/j.cogc.2014.02.002

Rizzuto, I., Stavraka, C., Chatterjee, J., Borley, J., Hopkins, T. G., Gabra, H., Ghaem-Maghami, S., Huson, L., & Blagden, S. P. (2015). Risk of ovarian cancer relapse score: A prognostic algorithm to predict relapse following treatment for advanced ovarian cancer. International Journal of Gynecological Cancer, 25(3), 416–422. https://doi.org/10.1097/IGC.0000000000000361

Bacalbasa, N., Dima, S., Balescu, I., David, L., Brasoveanu, V., & Popescu, I. (2015). Results of Primary Cytoreductive Surgery in Advanced-stage Epithelial Ovarian Cancer : A Single-center Experience. 4104, 4099–4104.

Cuylan, Z. F., Meydanli, M. M., Sari, M. E., Akbayir, O., Celik, H., Dede, M., Sahin, H., Gungorduk, K., Kuscu, E., Ozgul, N., Gungor, T., & Ayhan, A. (2018). Prognostic factors for maximally or optimally cytoreduced stage III nonserous epithelial ovarian carcinoma treated with carboplatin / paclitaxel chemotherapy. 1–10. https://doi.org/10.1111/jog.13663

Corrado, G., Salutari, V., Palluzzi, E., Distefano, M. G., Scambia, G., & Ferrandina, G. (2017). ovarian cancer ce pt t. Expert Review of Anticancer Therapy, 0(0). https://doi.org/10.1080/14737140.2017.1398088

Vargas-Hernández, V. M., Moreno-Eutimio, M. A., Acosta-Altamirano, G., & Vargas-Aguilar, V. M. (2014). Management of recurrent epithelial ovarian cancer. Gland Surgery, 3(3), 198–202. https://doi.org/10.3978/j.issn.2227-684X.2013.10.01



DOI: https://doi.org/10.22146/jkr.69698

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