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

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.

Keywords: CXCR4; Chemotherapy; Metastasis; breast cancer; mRNA SDF1a.

Figure 1

(a). Low nuclear expression, (b). High nuclear expression, (c). Low cytoplasmic expression, (d) High cytoplasmic expression

Figure 2

Time from Diagnosis to Distant Metastasis Determined by Cytoplasmic CXCR4. (a) In the all-patient group, the cytoplasmic CXCR4 expression showed a non-significant to correlation to metastasis. (b) However, the non-chemotherapy group showed a significant difference in high cytoplasmic CXCR4 expression with a worse metastasis. (c) Meanwhile, in the complete-chemotherapy group, there was no difference in high and low cytoplasmic CXCR4

Figure 3

Time from Diagnosis to Distant Metastasis Determined by SDF1a. (a) In the all-patient group, SDF1a high amplification showed a significantly shorter metastasis time. (b) Likewise, the non-chemotherapy group showed a significant difference. (c) Interestingly in the complete-chemotherapy group, there was no difference in high and low SDF1a amplification toward to metastasis

Figure 4

Kaplan–Meier Chart of Cytoplasmic CXCR4 to Overall Survival in All 3 Patient Groups. (a) High cytoplasmic CXCR4 expression showed shorter metastatic time although it was not significant in the all-patient group. (b) High cytoplasmic CXCR4 expression in the no chemotherapy group showed a significant difference in the poor OS with P = 0.010. (c) But interestingly complete-chemotherapy group showed no significant difference between high and low cytoplasmic CXCR4 expressions

Figure 5

Kaplan–Meier Chart of SDF1a to Overall Survival in All 3 Patient Groups. (a) The SDF1 amplification showed a no significant OS in the all-patient group. (b) High expression of SDF 1 in no-chemotherapy group had significantly different OS. (c) Complete-chemotherapy group showed no significant difference between high and low SDF1a