# Exploratory study linking plasma proteomics to cardiotoxicity in Hodgkin lymphoma

## TL;DR

This study explores how certain proteins in the blood may predict heart problems in Hodgkin lymphoma patients after treatment.

## Contribution

The study identifies three new plasma protein biomarkers associated with cardiovascular disease in Hodgkin lymphoma survivors.

## Key findings

- CYR61, GPNMB, and ALCAM proteins are significantly linked to heart failure and ischemic heart disease in Hodgkin lymphoma patients.
- The study suggests these biomarkers could improve risk prediction for cardiovascular events in this patient population.
- Protein analysis was conducted using plasma samples collected before, during, and after treatment.

## Abstract

Cardiovascular toxicity is a well-known complication of chemotherapy, especially doxorubicin (DXR), and irradiation of the mediastinum for classical Hodgkin lymphoma (cHL). Due to the excellent prognosis in cHL, the mortality rate in late toxicity historically exceeds that of relapse of lymphoma. This highlights the need for strategies to minimize toxicity.Our aim was to characterize the prevalence of cardiovascular diseases (CVDs) in our cohort of cHL patients treated with DXR with or without radiotherapy according to standard practice and to identify any plasma protein associations with preexisting or emerging CVD posttreatment.

We analyzed 182 different proteins in plasma samples from 56 cHL patients and 60 controls using Olink multiplex protein panels Oncology II and Cardiovascular III. The analysis was supplemented with separate analyses of N-terminal pro-brain natriuretic peptide (NTpro-BNP), troponin I and C-reactive protein (CRP). The patient samples were prospectively collected prior to, during and after treatment.

Our analysis revealed a statistically significant association between the compound endpoint of heart failure and ischemic heart disease and the protein biomarkers cysteine rich protein 61 (CYR61), glycoprotein nonmetastatic melanoma protein B (GPNMB) and activated leukocyte cell adhesion molecule (ALCAM) in samples collected after treatment for cHL.

This exploratory study identified three new biomarkers reflecting different biological processes associated with CVD in patients treated for cHL. Adding biomarkers to risk prediction in this population has the potential to identify patients with a high risk of cardiovascular events who need focused follow-up.

The online version contains supplementary material available at 10.1186/s40959-025-00426-2.