Chemotherapy Negates the Effect of SDF1 mRNA to Distant Metastasis and Poor Overall Survival in Breast Cancer Patients

Document Type: Research Articles

Authors

1 Department of Surgery, Oncology Division, Medical Faculty, Sebelas Maret University, Indonesia.

2 Department of Surgery, Medical Faculty, Sebelas Maret University, Indonesia.

3 Department of Public Health, Faculty of Public Health, Veteran Bangun Nusantara Sukoharjo University, Indonesia.

4 Department of Anatomical Pathology, Medical Faculty, Sebelas Maret University, Indonesia.

5 Department of Anatomical Pathology, Medical Faculty, Gadjah Mada University, Indonesia.

6 Department of Pharmacology and Therapy, Medical Faculty, Gadjah Mada University, Indonesia.

7 Department of Obstetrics and Gynecology, Medical Faculty, Gadjah Mada University, Indonesia.

8 Department of Surgery, Oncology Division, Medical Faculty, Gadjah Mada University, Indonesia.

Abstract

Objective: Investigate the effect of SDF1a, nuclear, and cytoplasmic CXCR4 breast cancer tissue on metastasis and overall survival in patients with complete-chemotherapy and no-chemotherapy. Methods: Cohort ambidirectional design was employed with survival analysis that followed the patient’s diagnosis until obtaining the outcome, distant metastasis, or death. We analyzed samples in three groups (all-patient, no-chemotherapy, and complete-chemotherapy groups).  Breast cancer cell nuclear and cytoplasm expressions of CXCR4 protein were examined using immunohistochemistry. Amplification of mRNA SDF1a of breast cancer tissue was examined using rtPCR on 131 samples from the same initial paraffin block. Results: In the distant metastasis and Overall Survival (OS) analysis, there was no correlation between cytoplasmic and nuclear CXCR4 in all-patient, no-chemotherapy, and complete-chemotherapy groups. SDF1a was significantly correlated to shorter distant metastasis and poor OS in the all-patient (p=0.004 and p=0.04, respectively) and no-chemotherapy group (p=0.008 and p=0.026, respectively). However, in the complete-chemotherapy group, SDF1a was not correlated to either metastasis (p=0.527) or OS (p=0.993), advanced stage demonstrated a strong association on shorter distant metastatic in no-chemotherapy (p=0.021) and complete-chemotherapy group (p=0.004) and also poor OS in both groups (p=0.006 and p=0.002, respectively). The hormone receptor showed a protective effect on the no-chemotherapy group’s OS (p= 0.019). Meanwhile, not undergoing chemotherapy was associated with poor OS in the all-patient group (p= 0.011). Conclusion: SDF1a mRNA amplification has a significant correlation with the occurrence of metastasis and OS in all-patient and no-chemotherapy group. Undergoing chemotherapy negates the effect of SDF1a for distant metastasis and OS.

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