Biomarker panel for early screening of trastuzumab -induced cardiotoxicity among breast cancer patients in west virginia

Figures

• 

  FIGURE 1. Assessment of plasma biomarkers. Quantitative analysis of plasma biomarker concentrations by ELISA: (A) cardiac troponin I, (B) cardiac troponin T, (C) placental growth factor (PIGF), (D) cardiac myosin light chain 1 (cMLC1), (E) growth differentiation factor 15 (GDF-15). Values represent means ± SEM. *p < 0.05 vs. Control, **p < 0.01 vs. Control, #p < 0.05 vs. Baseline, ##p < 0.01 vs. Baseline.

• 

  FIGURE 2. Assessment of circulating plasma miRNA expression. Quantitative analysis of circulating plasma miRNA expression by qRT-PCR: (A) miR-34a, (B) miR-21, (C) miR-133, (D) miR-1, (E) miR-30e. Values represent means ± SEM. *p < 0.05 vs. Control, **p < 0.01 vs. Control, #p < 0.05 vs. Baseline, ##p < 0.01 vs. Baseline.

• 

  FIGURE 3. Correlation analysis of cardiac troponin I with plasma biomarkers. Correlation analysis was performed using a scatter plot between cardiac troponin I and plasma biomarkers, (A) cardiac myosin light chain 1 (cMLC1), (B) growth differentiation factor 15 (GDF-15) and (C) placental growth factor (PIGF). Pearson’s r coefficient was used to determine the extent of correlation and statistical significance was obtained by two-tailed p-value. Each plot independently demonstrates the correlation (Pearson’s r coefficient) and significance (p—value).

• 

  FIGURE 4. Correlation analysis of cardiac troponin I with circulating plasma miRNAs. Correlation analysis was performed using a scatter plot between cardiac troponin I and plasma miRNAs, (A) miR-34a, (B) miR-21, (C) miR-133, (D) miR-1, (E) miR-30e. Pearson’s r coefficient was used to determine the extent of correlation and statistical significance was obtained by two-tailed p-value. Each plot independently demonstrates the correlation (Pearson’s r coefficient) and significance (p—value).

• 

  FIGURE 5. Correlation analysis of cardiac troponin T with plasma biomarkers. Correlation analysis was performed using a scatter plot between cardiac troponin T and plasma biomarkers, (A) cardiac myosin light chain 1 (cMLC1), (B) growth differentiation factor 15 (GDF-15) and (C) placental growth factor (PIGF). Pearson’s r coefficient was used to determine the extent of correlation and statistical significance was obtained by two-tailed p-value. Each plot independently demonstrates the correlation (Pearson’s r coefficient) and significance (p—value).

• 

  FIGURE 6. Correlation analysis of cardiac troponin T with circulating plasma miRNAs. Correlation analysis was performed using a scatter plot between cardiac troponin T and plasma miRNAs, (A) miR-34a, (B) miR-21, (C) miR-133, (D) miR-1, (E) miR-30e. Pearson’s r coefficient was used to determine the extent of correlation and statistical significance was obtained by two-tailed p-value. Each plot independently demonstrates the correlation (Pearson’s r coefficient) and significance (p—value).

• 

  FIGURE 7. Schematic representation demonstrating the progression of trastuzumab induced cardiotoxicity. Chemotherapeutic regimen, trastuzumab, specifically inhibits the human epidermal growth factor receptor 2 (HER2) receptor to negate the cancerous cell growth and survival, as a mechanism of action. However, trastuzumab treatment upregulates the expression of plasma biomarkers and circulating miRNA, that are primarily involved in the regulation of cardiac function. The mechanistic action of trastuzumab induces cardiotoxicity by cardiomyocyte damage, cardiac fibrosis, LVEF decline, oxidative stress and cellular apoptosis. Since the panel of proposed biomarkers and miRNAs is specifically involved in the cardiac remodeling and regulation of cardiac function, their upregulated expression can predict cardiotoxicity before it is apparent on echocardiography. Hence, the utility of the proposed panel in clinical practice is viable for the early prognosis of trastuzumab induced cardiotoxicity.