Article Main

Serum CCL2 and CXCL8 Levels in Breast Cancer Patients Undergoing Treatment in Karbala, Iraq: Associations with Hormonal Receptor Status and Therapeutic Modalities Serum CCL2 and CXCL8 Levels

Intisar Mohammed Kashash
Kiaser Abdulsajjad M. Hussain
Alaa Hussein Mahdi
Journal of Progressive Medical Sciences, Vol. 2 No. 5 (2026): Fifth issue - May 2026
Published: 2026-05-31

Abstract

Background: Breast cancer is among the most prevalent cancers amongst females and is strongly related to inflammatory reactions in the tumor microenvironment. The role of chemokines such as CCL2 and CXCL8 in the development of tumor cells, tumor angiogenesis, and immune system modulation is well established. objective: The current study aimed to assess serum concentrations of CCL2 and CXCL8 chemokines in breast cancer patients under treatment in Karbala governorate, Iraq, and the correlation with hormonal receptor HER2, ER, PR status and treatment strategies. Methodology: A case-control design was carried out on 60 breast cancer patients and 40 healthy subjects. Blood samples were taken from patients during their treatment, and full blood count was conducted. Measurement of serum concentrations of CCL2 and CXCL8 was done using sandwich ELISA method. Statistical analysis was performed using SPSS program version 25, and p ≤ 0.05 was considered statistically significant. Results: The outcomes indicate that there was a remarkable difference in chemokine serum concentrations between breast cancer patients and controls. Serum concentration of CCL2 was considerably lower than that in the control group in some molecular subtypes while the serum concentration of CXCL8 was significantly higher in breast cancer patients (p = 0.012). There was a significant association between chemokine concentration and HER2, ER, and PR receptor status. Significantly higher concentrations of CCL2 and CXCL8 were also highly correlated with the treatment strategy, with the maximum concentration being observed in those treated with chemotherapy and radiotherapy (p ≤ 0.001). High positive correlations between CCL2 and CXCL8 were established. The above findings show that CCL2 and CXCL8 have an important role in the inflammatory microenvironment of breast cancer. CXCL8 concentration is constantly higher in breast cancer patients while CCL2 concentration varies according to the receptor status and treatment type. Conclusions: CXCL8 may be used as a stable biomarker for systemic inflammation in breast cancer patients undergoing treatment. CCL2 levels are affected by hormone receptor status and the type of treatment. Further longitudinal studies are needed to evaluate its diagnostic and prognostic potential.

Keywords

Array Array Array Array Array Array Array Array Array

References

  1. 1. LL Wilkinson and T. Gathani, “Understanding breast cancer as a global health concern 1 1,” no. September 2021, pp. 7–9, 2022.
  2. 2. A. Nishida, “The Role of Inflammation in Cancer : Mechanisms of Tumor Initiation , Progression , and Metastasis,” 2025.
  3. 3. H. Li, Role of chemokine systems in cancer and inflammatory diseases, no. May. 2022. doi: 10.1002/mco2.147.
  4. 4. S. Kadomoto, “Roles of CCL2-CCR2 Axis in the Tumor Microenvironment,” 2021.
  5. 5. X. Xiong, X. Liao, S. Qiu, H. Xu, S. Zhang, and S. Wang, “CXCL8 in Tumor Biology and Its Implications for Clinical Translation,” vol. 9, no. March, pp. 1–13, 2022, doi: 10.3389/fmolb.2022.723846.
  6. 6. J. Jin et al., “CCL2 : An Important Mediator Between Tumor Cells and Host Cells in Tumor Microenvironment,” vol. 11, no. July, pp. 1–14, 2021, doi: 10.3389/fonc.2021.722916.
  7. 7. J. Wang et al., “Expression of CCL2 is significantly different in five breast cancer genotypes and predicts patient outcome,” vol. 8, no. 9, pp. 15684–15691, 2015.
  8. 8. G. Soria and A. Ben-baruch, “The inflammatory chemokines CCL2 and CCL5 in breast cancer,” vol. 267, pp. 271–285, 2008, doi: 10.1016/j.canlet.2008.03.018.
  9. 9. A. Mishra, K. Hassan, S. Nisha, N. Jaseela, and M. Vishwas, “An updated review on the role of the CXCL8 ‑ CXCR1 / 2 axis in the progression and metastasis of breast cancer,” Mol. Biol. Rep., no. 0123456789, 2021, doi: 10.1007/s11033-021-06648-8.
  10. 10. C. Parra-l, “Critical Reviews in Oncology / Hematology A review concerning the breast cancer-related tumour microenvironment,” vol. 199, no. April, 2024, doi: 10.1016/j.critrevonc.2024.104389.
  11. 11. H. A. Zainalbden, E. Arslan, and I. E. Alsaimary, “Expression analysis of CCL2 , CCL5 , and CXCL10 in breast cancer : an insight into the inflammatory microenvironment,” vol. 29, no. September, pp. 513–519, 2025, doi: 10.35975/apic.v29i6.2901.
  12. 12. B. Smolarz, A. Zadro, and H. Romanowicz, “Treatment ( Review of Literature ),” pp. 1–27, 2022.
  13. 13. A. Dehghani, “The Immunoregulatory Roles of ER α in Breast Cancer : Mechanisms , Crosstalk , and Therapeutic Insights,” vol. 31, no. 1, pp. 1–10, 2026.
  14. 14. M. Masrour, A. Moeinafshar, A. Poopak, S. Razi, and N. Rezaei, “The role of CXC chemokines and receptors in breast cancer,” Clin. Exp. Med., vol. 25, no. 1, pp. 1–22, 2025, doi: 10.1007/s10238-025-01662-7.
  15. 15. R. Qin et al., “Role of chemokines in the crosstalk between tumor and tumor ‑ associated macrophages,” Clin. Exp. Med., vol. 23, no. 5, pp. 1359–1373, 2023, doi: 10.1007/s10238-022-00888-z.
  16. 16. Y. Lv et al., “CXCL2 : a key player in the tumor microenvironment and inflammatory diseases,” 2025.
  17. 17. S. Cambier, “The chemokines CXCL8 and CXCL12 : molecular and functional properties , role in disease and efforts towards pharmacological intervention,” no. July 2022, 2023, doi: 10.1038/s41423-023-00974-6.
  18. 18. B. T. Surgery, L. Clinical, and J. Province, “High CXCL8 expression predicting poor prognosis in triple-negative breast cancer,” pp. 246–252, 2025, doi: 10.1097/CAD.0000000000001678.
  19. 19. Y. Hou, J. Li, Q. Zhang, and Y. Fan, “Association of progesterone receptor status with breast cancer prognosis : a meta-analysis,” 2025.
  20. 20. A. G. L. Mbbch, M. S. T. Mbbch, N. P. M. Hons, A. R. G. Hons, and E. A. R. Mbbch, “The clinical value of progesterone receptor expression in luminal breast cancer: A study of a large cohort with long ‐ term follow ‐ up,” no. December 2022, pp. 1183–1194, 2023, doi: 10.1002/cncr.34655.
  21. 21. S. Stępień et al., “Clinical significance of the CXCL8 / CXCR1 / R2 signalling axis in patients with invasive breast cancer,” pp. 1–9, 2024, doi: 10.3892/ol.2024.14393.
  22. 22. K. B. Horwitz and C. A. Sartorius, “Progesterone and Progesterone Receptors in Breast Cancer: Past, Present, Future,” vol. 65, no. 1, pp. 1–22, 2021, doi: 10.1530/JME-20-0104.Progesterone.
  23. 23. L. Wang, J. Jiang, Y. Chen, Q. Jia, and Q. Chu, “The roles of CC chemokines in response to radiation,” Radiat. Oncol., pp. 1–12, 2022, doi: 10.1186/s13014-022-02038-x.
  24. 24. J. Xu et al., “Dual roles and therapeutic targeting of tumor-associated macrophages in tumor microenvironments,” no. March, 2025.
  25. 25. S. Pathway, “Roles of the CXCL8-CXCR1 / 2 Axis in Cancer,” vol. 8, pp. 1–14.
  26. 26. Z. Shi et al., “CC Chemokine Ligand-2 : A Promising Target for Overcoming Anticancer Drug Resistance,” pp. 1–15, 2022.
  27. 27. A. Rahman, T. A. Rahman, S. Ghosh, S. M. Badar, A. Nazir, and G. B. Bamigbade, “The paradoxical role of cytokines and chemokines at the tumor microenvironment : a comprehensive review,” Eur. J. Med. Res., pp. 1–19, 2024, doi: 10.1186/s40001-024-01711-z.
  28. 28. A. J. Ozga, M. T. Chow, and A. D. Luster, “Review Chemokines and the immune response to cancer,” Immunity, vol. 54, no. 5, pp. 859–874, 2021, doi: 10.1016/j.immuni.2021.01.012.

Author Biography

Intisar Mohammed Kashash
None
Kiaser Abdulsajjad M. Hussain
None
Alaa Hussein Mahdi
None
PDF
Download PDF

Article Details