Upregulation of Endothelin-1 May Predict Chemotherapy-Induced Cardiotoxicity in Women with Breast Cancer

Figure 1. From initial 175 patients that were identified, 52 met eligibility criteria. However, sample that could be used for immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) was only present for 33 samples. Patients with CIC (n = 14) were compared to those without CIC (n = 19) in analyses.

Figure 2. Expression of ET1, Big ET1 and ATR1 staining in breast tumor tissue. (A) Representative photo of IHC showing positive staining for ET1 (red arrow). (B) Representative photo of IHC showing positive staining for Big ET1 (red arrow). (C) Representative photo of IHC staining for ATR1 (red arrow). (D) Mean positive immunohistochemistry staining (%) for ET1, Big ET1 and ATR1 in breast tumor tissue normalized to the tumor tissue area. n = 33, ****, p < 0.0001.

Figure 3. Relationship between LVEF of >55% or ≤50% and ET1 in tumor samples. (A) Relative gene expression (RGE) of ET1 by qRT-PCR (* p = 0.031) compared to the housekeeping gene PUM1. (B) Pearson correlation for ET1 RGE vs. percentage of LVEF showing greater ET1 expression with lower LVEF (* p = 0.032). n = 25.

Figure 4. Relationship between change in percentage of LVEF <10% or ≥10% and ET1 expression level. (A) Relative gene expression (RGE) of ET1 by qRT-PCR (* p = 0.026) compared to the housekeeping gene PUM1. (B) Pearson correlation for ET1 expression with change in percentage of LVEF showing more ET1 expression with greater change in LVEF (* p = 0.017). n = 25.

Figure 5. Relationship between LVEF of >55% or ≤50% and ET1 Receptor A in tumor samples. (A) Relative gene expression (RGE) of ET1 receptor A by qRT-PCR (p = 0.1837) compared to the housekeeping gene PUM1. (B) Pearson correlation for ET1 Receptor A vs. percentage of LVEF (p = 0.161). n = 22.

Figure 6. Relationship between change in percentage of LVEF <10% or ≥10% and ET1 Receptor A. (A) Relative gene expression (RGE) of ET1 receptor A by qRT-PCR (p = 0.248) compared to the housekeeping gene PUM1. (B) Pearson correlation for ET1 Receptor A expression vs. change in percentage of LVEF (p = 0.564). n = 20.

Figure 7. Relationship between LVEF of >55% or ≤50% and ET1 Receptor B in tumor samples. (A) Relative gene expression (RGE) of ET1 receptor B by qRT-PCR (p = 0.181) compared to the housekeeping gene PUM1. (B) Pearson correlation for ET1 Receptor B vs. percentage of LVEF (p = 0.354). n = 13.

Figure 8. Relationship between change in percentage of LVEF <10% or ≥10% and ET1 Receptor B. (A) Relative gene expression (RGE) of ET1 receptor B by qRT-PCR (p = 0.242) compared to the housekeeping gene PUM1. (B) Pearson correlation for ET1 Receptor B expression vs. change in percentage of LVEF (p = 0.954). n = 12.

Figure 9. Relationship between LVEF of >55% or ≤50% and ATR1 in tumor samples. (A) Relative gene expression (RGE) of ATR1 by qRT-PCR (p = 0.379) compared to the housekeeping gene PUM1. (B) Pearson correlation for ATR1 vs. percentage of LVEF showing no significant relationship between ATR1 expression and percentage of LVEF (p = 0.404). n = 13.

Figure 10. Relationship between change in percentage of LVEF <10% or ≥10% and ATR1. (A) Relative gene expression (RGE) of ATR1 by qRT-PCR (p = 0.153) compared to the housekeeping gene PUM1. (B) Pearson correlation for ATR1 expression vs. change in percentage of LVEF (p = 0.247). n = 13.