International Journal of Medical Science and Pharmaceutical Research

The heterogeneity of biology in breast cancer and the drawbacks of traditional diagnosing strategies such as imaging and invasive biopsy have remained as obstacles to an early diagnosis and an accurate prognosis prediction. Non-invasive biomarkers for the diagnosis of breast carcinoma are thus highly desirable. Heat shock protein 90 (Hsp90) is a molecular chaperone which is responsible for the stabilization and maturation of many oncogenic proteins, and has become one of the representative cancer biomarkers. Herein we investigated the prediction and diagnostic value of circulating Hsp90 for breast carcinoma. Patients and Methods: A cross-sectional diagnostic study was performed at the Al-Forat Al-Awsat Oncology Center in Al-Najaf City, Iraq between March 2025 to September 2025. The patients studied comprised 125 suspected cases of breast carcinoma and 75 apparently normal controls. Plasma levels of Hsp90 before any therapeutic intervention were quantified by enzyme linked immunosorbent assay (ELISA). The diagnosis was further confirmed by histopathology and breast imaging as the gold standard. Predictive and diagnostic performance of Hsp90 was evaluated using logistic regression and ROC (receiver operating characteristic) curve analysis. Results: Serum Hsp90 levels were significantly higher in breast carcinoma patients than in healthy subjects (p < 0.003). Logistic regression analysis was performed demonstrating Hsp90 as an independent factor for breast cancer (odds ratio = 6.49, 95 % CI: 2.69–15.63; P < 0.001). Then, the ROC curve analysis showed good diagnostic performance of AUC = 0.89 with a sensitivity of 85.6% and specificity of 82.3% in optimal cut-off value. Conclusions: Circulating Hsp90 appears to be a promising non-invasive pre- and clinical marker for the prediction and diagnosis of breast carcinoma, which can help in diagnosis for early detection and decision making.

Hsp90, Breast Tumors, Chaperone, Sensitivity, Specificity

1. Addai Ali, H., Mueen Hassoun, S., Alkadhim Abd, M. A., Saleh Mashkour, M., Adday Ali, R., & Kadhim Alyaseen, M. (2025). Evaluation of Heat Shock Protein-90 as a Potential Risk Marker in Sera Women with Breast Cancer. Asian Pacific Journal of Cancer Biology, 10(3), 735-740. https://doi.org/10.31557/apjcb.2025.10.3.735-740
2. Ali A. H., Hassoun, S. M., Alkadhim Abd, M. A., Mashkour, M. S., Adday Ali, R., & Alyaseen, M. K. (2025). Evaluation of heat shock protein-90 as a potential risk marker in sera women with breast cancer. Asian Pacific Journal of Cancer Biology, 10(3), 735–740. https://doi.org/10.31557/apjcb.2025.10.3.735-740
3. Birbo, B., Madu, E. E., Madu, C. O., Jain, A., & Lu, Y. (2021). Role of HSP90 in Cancer. International journal of molecular sciences, 22(19), 10317. https://doi.org/10.3390/ijms221910317
4. Cheng, Q., Chang, J. T., Geradts, J., Neckers, L. M., Haystead, T., Spector, N. L., & Lyerly, H. K. (2012). Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer. Breast cancer research : BCR, 14(2), R62. https://doi.org/10.1186/bcr3168 
5. Chiba, Y., Saito, K., Yamaguchi, A., Shimizu, K., Iwase, K., Ueno, S., & Inokuchi, M. (2016). High mobility group box 1 and heat shock protein 90 as predictors of metastasis in patients with colorectal cancer. World Journal of Gastroenterology, 22(41), 9163–9173. https://doi.org/10.3748/wjg.v22.i41.9163
6. Deng, Y., Li, F., Hu, Z., Yue, C., & Tang, Y. Z. (2021). Expression Patterns of the Heat Shock Protein 90 (Hsp90) Gene Suggest Its Possible Involvement in Maintaining the Dormancy of Dinoflagellate Resting Cysts. International Journal of Molecular Sciences, 22(20), 11054. https://doi.org/10.3390/ijms222011054
7. Dimas, D. T., Perlepe, C. D., Sergentanis, T. N., Misitzis, I., Kontzoglou, K., Patsouris, E., Kouraklis, G., Psaltopoulou, T., & Nonni, A. (2018). The Prognostic Significance of Hsp70/Hsp90 Expression in Breast Cancer: A Systematic Review and Meta-analysis. Anticancer research, 38(3), 1551–1562. https://doi.org/10.21873/anticanres.12384
8. Kamal, A., Boehm, M. F., & Burrows, F. J. (2004). Therapeutic and diagnostic implications of Hsp90 activation. Trends in molecular medicine, 10(6), 283–290. https://doi.org/10.1016/j.molmed.2004.04.006
9. Lin, T., Qiu, Y., Peng, W., & Peng, L. (2020). Heat Shock Protein 90 Family Isoforms as Prognostic Biomarkers and Their Correlations with Immune Infiltration in Breast Cancer. BioMed research international, 2020, 2148253. https://doi.org/10.1155/2020/2148253
10. Liu, H., Zhang, Z., Huang, Y., Wei, W., Ning, S., Li, J., Liang, X., Liu, K., & Zhang, L. (2021). Plasma HSP90AA1 Predicts the Risk of Breast Cancer Onset and Distant Metastasis. Frontiers in cell and developmental biology, 9, 639596. https://doi.org/10.3389/fcell.2021.639596
11. Pick, E., Kluger, Y., Giltnane, J. M., Moeder, C., Camp, R. L., Rimm, D. L., & Kluger, H. M. (2007). High HSP90 expression is associated with decreased survival in breast cancer. Cancer research, 67(7), 2932–2937. https://doi.org/10.1158/0008-5472.CAN-06-4511 
12. Rastogi, S., Joshi, A., Sato, N., Lee, S., Lee, M. J., Trepel, J. B., & Neckers, L. (2024). An update on the status of HSP90 inhibitors in cancer clinical trials. Cell stress & chaperones, 29(4), 519–539. https://doi.org/10.1016/j.cstres.2024.05.005
13. Sahan, K., Zahraa Abbas Sahan, & Haidar Al Qazzaz. (2025). Predictive Power of Multiplex Serum Biomarkers in Breast Cancer: A Comprehensive ROC Curve Analysis. Iraqi Journal of Cancer and Medical Genetics, 18(2). https://doi.org/10.29409/zvqcs091
14. Siebert, C., Ciato, D., Murakami, M., Frei-Stuber, L., Perez-Rivas, L. G., Monteserin-Garcia, J. L., Nölting, S., Maurer, J., Feuchtinger, A., Walch, A. K., Haak, H. R., Bertherat, J., Mannelli, M., Fassnacht, M., Korpershoek, E., Reincke, M., Stalla, G. K., Hantel, C., & Beuschlein, F. (2019). Heat Shock Protein 90 as a Prognostic Marker and Therapeutic Target for Adrenocortical Carcinoma. Frontiers in endocrinology, 10, 487. https://doi.org/10.3389/fendo.2019.00487
15. Wei, H., Zhang, Y., Jia, Y., Chen, X., Niu, T., Chatterjee, A., He, P., & Hou, G. (2024). Heat shock protein 90: biological functions, diseases, and therapeutic targets. MedComm, 5(2), e470. https://doi.org/10.1002/mco2.470
16. Wei, W., Liu, M., Ning, S., Wei, J., Zhong, J., Li, J., Cai, Z., & Zhang, L. (2020). Diagnostic value of plasma HSP90α levels for detection of hepatocellular carcinoma. BMC cancer, 20(1), 6. https://doi.org/10.1186/s12885-019-6489-0
17. Wikipedia. (2025). Hsp90. Retrieved from https://en.wikipedia.org/wiki/Hsp90
18. Zagouri, F., Bournakis, E., Koutsoukos, K., & Papadimitriou, C. A. (2012). Heat Shock Protein 90 (Hsp90) Expression and Breast Cancer. Pharmaceuticals, 5(9), 1008-1020. https://doi.org/10.3390/ph5091008 
19. Zagouri, F., Sergentanis, T. N., Chrysikos, D., Papadimitriou, C. A., Dimopoulos, M. A., & Psaltopoulou, T. (2013). Hsp90 inhibitors in breast cancer: a systematic review. Breast (Edinburgh, Scotland), 22(5), 569–578. https://doi.org/10.1016/j.breast.2013.06.003 
20. Zhao, Q., Miao, C., Lu, Q., Wu, W., He, Y., Wu, S., Liu, H., & Lian, C. (2021). Clinical Significance of Monitoring Circulating Free DNA and Plasma Heat Shock Protein 90alpha in Patients with Esophageal Squamous Cell Carcinoma. Cancer management and research, 13, 2223–2234. https://doi.org/10.2147/CMAR.S295927