Galectin-3 and Myeloperoxidase May Monitor Cancer-Therapy-Related Cardiotoxicity? A Systematic Review and Meta-Analysis

Abstract

Galectin-3 and myeloperoxidase (MPO) are novel biomarkers in the field of cardio-oncology, but conflicting results have been reported. Hence, a meta-analysis was performed to assess the monitoring value of galectin-3 and MPO in cancer-therapy-related cardiotoxicity. PubMed, Cochrane, Web of Science, Embase, CNKI databases and ClinicalTrials.gov were queried. According to the predefined inclusion and exclusion criteria, eight studies with 1979 patients were included in this meta-analysis. The examination of the study's heterogeneity (I²), quality assessment and statistical analysis were performed by two reviewers. No significant differences in galectin-3 levels were noted before and after treatment (WMD = -0.10, 90% CI -6.06-5.85, I²: 99%), and a weaker relationship was observed between galectin-3 evaluations and cancer-therapy-related cardiotoxicity (HR = 1.39, 90% CI 0.97-1.98, I²: 0%). However, MPO levels were increased in patients post-treatment (SMD = 0.58, 90% CI 0.35-0.80, I²: 56%), and an increased risk of cardiotoxicity was associated with early pre-post MPO assessments (HR = 1.16, 90% CI 1.02-1.32, I²: 21%). Surprisingly, the MPO levels were a more effective indicator of the response to tumor treatment compared with the TnI (SMD = 2.46, 90% CI -0.26-5.19, I²: 96%) and NT-proBNP levels (SMD = 1.08, 90% CI -0.82-2.98, I²: 96%). In conclusion, our meta-analysis suggests that MPO may rep-resent a potential biomarker for the early detection of cardiotoxicity in current cardio-oncology practice, but the monitoring value of galectin-3 requires further study.

Keywords: biomarker; cancer therapy; cardio-oncology; cardiotoxicity; galectin-3; myeloperoxidase.

Figure 1

PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only.

Figure 2

Quality assessment using the Newcastle-Ottawa Scale for cohort studies [13,14,15,16,17,18,19,20].

Figure 3

Overall and individual study estimates of the weighted mean difference of Galectin-3 are shown in patients receiving cancer treatment. Parallelogram boxes for weighted mean difference and horizontal lines represent 90% confidence interval (CI). Subgroup analyses were carried out independently for country (A), the presence of doxorubicin (B) and measurement (C) [14,15,17,18,19].

Figure 3

Overall and individual study estimates of the weighted mean difference of Galectin-3 are shown in patients receiving cancer treatment. Parallelogram boxes for weighted mean difference and horizontal lines represent 90% confidence interval (CI). Subgroup analyses were carried out independently for country (A), the presence of doxorubicin (B) and measurement (C) [14,15,17,18,19].

Figure 4

Cancer-therapy-related cardiotoxicity as measured by a standardized left ventricular ejection fraction decrease with no considerable Galectin-3 change. Parallelogram boxes for hazard ratio, and horizontal lines represent 90% confidence interval (CI) [15,19].

Figure 5

(A) Overall and individual study estimates of the standardized mean difference of MPO are shown in patients receiving cancer treatment. Parallelogram boxes for standardized mean difference, and horizontal lines represent 90% confidence interval (CI). (B) Cancer-therapy-related cardiotoxicity as measured by a standardized left ventricular ejection fraction decrease with significant MPO change. Parallelogram boxes for hazard ratio, and horizontal lines represent 90% confidence interval (CI) [13,16,17,19,20].

Figure 6

The potential mechanism of MPO increasing after cancer therapy. MPO: myeloperoxidase; NETs: neutrophil extracellular traps.