Correlation Between Blood Transforming Growth Factor-Beta 1 (TGF-β1) Levels and Cardiac Function Parameters Following...

Doxorubicin is an anthracycline-based chemotherapeutic agent that is effective against various malignancies. However, it is associated with significant cardiotoxic side effects, which may lead to a reduction in ejection fraction (EF), tricuspid annular plane systolic excursion (TAPSE), early (E) to late (A) diastolic filling velocities (E/A), early mitral inflow velocity and mitral annular early diastolic velocity (E/E'), and myocardial dysfunction as measured by global longitudinal strain (GLS). Transforming growth factor-beta 1 (TGF-β1) is a proinflammatory cytokine that plays a key role in cardiac fibrotic remodeling and is suspected to contribute to the pathogenesis of doxorubicin-induced cardiotoxicity. Currently, human studies investigating the association between TGF-β1 levels and cardiac function deterioration due to doxorubicin remain limited. The objective of this study is to assess the correlation between serum TGF-β1 levels and EF, E/A, E/E', TAPSE, and GLS in cancer patients 3-12 months after completing full-course doxorubicin chemotherapy, as cardiotoxicity often occurs less than 12 months after chemotherapy.

This research employed a cross-sectional design. Subjects included cancer patients who completed full-course doxorubicin chemotherapy at Cipto Mangunkusumo General Hospital and Dharmais National Cancer Hospital, and who met the inclusion and exclusion criteria. Serum TGF-β1 levels were measured between the third and 12th month post-chemotherapy, concurrently with cardiac function evaluation via echocardiography to assess EF, E/A, E/E', TAPSE, and GLS. Based on the sample size calculation, the minimum number of samples needed for this study is 55 patients. Correlation analysis was performed using Pearson or Spearman tests, depending on the data distribution. Correlation analysis was considered statistically significant if the p-value was less than 0.05.

A total of 56 patients were obtained for analysis. No significant correlations were found between TGF-β1 levels and EF (r = 0.308; p = 0.779), E/A (r = -0.034; p = 0.805), E/E' (r = 0.153; p = 0.259), TAPSE (r = 0.093; p = 0.494), or GLS (r = 0.052; p = 0.704) in analysis of all 56 patients. However, a significant correlation was observed between TGF-β1 and E/E' (r = 0.391; p = 0.033) in patients who received a cumulative doxorubicin dose ≥600 mg/m² (n = 30 patients).

This study found no significant correlations between TGF-β1 and EF, E/A, E/E', TAPSE, or GLS in the overall cohort. In patients who had received a cumulative doxorubicin dose ≥600 mg/m², TGF-β1 correlated significantly with E/E'. As a profibrotic cytokine, TGF-β1 contributes to myocardial fibrosis, increasing stiffness and filling pressures, which may be best captured by E/E' rather than systolic indices. These findings suggest that higher cumulative anthracycline exposure may enhance cardiotoxicity risk and highlight TGF-β1 as a potential biomarker of anthracycline-induced cardiac fibrosis.