The serum protein panel test can help determine the risk of cardiomyopathy in childhood cancer survivors

Early disease detection is beneficial to ensure the best possible outcomes for patients. However, finding noninvasive, effective methods to predict disease risk is an enormous challenge. Findings from scientists at St. Jude Children’s Research Hospital hold promise for assessing cardiomyopathy risk in childhood cancer survivors. Heart disease is a known late consequence in pediatric cancer survivors treated with anthracycline chemotherapy. The researchers identified a group of 27 proteins as biomarkers of cardiomyopathy risk, measured in blood serum. The study, which used data from the St. Jude Lifetime cohort (St. Jude LIFE), accurately predicted risk in 38 of 46 survivors, half with cardiomyopathy and half without. The results were published today in JACC: CardioOncology.

Anthracycline chemotherapy drugs such as doxorubicin, although highly effective in the treatment of solid and hematologic cancers in children, are known to increase the risk of cardiomyopathy. Heart muscle disease. Patients receiving anthracycline treatment can expect to be two to five times more likely to develop heart disease, with a five-year survival rate after diagnosis of less than 50%. Current methods for assessing cardiomyopathy risk in survivors, such as routine echocardiograms, are less effective for early detection because diagnosis typically occurs beyond the time of curative treatment.

Recognizing the need for an accurate and affordable cardiomyopathy prediction tool, Yadav Sapkota, PhD, St. Jude Department of Epidemiology & Cancer Control, sought to utilize the routine blood test. “We already measure proteins in regular laboratory tests, so this circulating biomarker test can be performed just as easily – a simple blood sample is all that is needed.”

“The goal is to more accurately identify asymptomatic people who are more likely to develop cardiomyopathy as they survive childhood cancer and then grow into adulthood,” he added.

A robust panel for detecting preclinical cardiomyopathy

Sapkota’s team studied participants in the St. Jude LIFE cohort. This ongoing study aims to comprehensively document the lifelong impact of childhood cancer through retrospective and prospective data collection and analysis. Researchers compared 98 survivors with cardiomyopathy with a comparable group without cardiomyopathy.

The aim was to identify “subclinical” cases of cardiomyopathy before symptoms appear. “75 of our samples had cardiomyopathy, but they showed no symptoms – which we call subclinical due to decreased cardiac function,” Sapkota explained. “We examined over 800 proteins in the patients who did not yet have symptoms and found 27 proteins that were differentially expressed in this group.”

The team examined whether this subset of proteins could be used to predict the risk of severe disease in an independent sample of survivors. “If we can use these proteins to predict who is likely to develop severe outcomes, we can then go back to asymptomatic patients or even those without compromised heart function and predict whether that person is likely to develop severe outcomes down the road.

Based on the pilot study, the research will be further expanded. “The plan is to assess circulating biomarkers for everyone in St. Jude LIFE – almost 5,000 people,” Sapkota said. “And while we have started with cardiomyopathy, we also want to evaluate other outcomes such as diabetes, second cancers and many others. This will be a great resource.”

Authors and funding

The first author of the study is Suresh Poudel, St. Jude. The study’s other authors are Cindy Im, University of Minnesota; Paul Burridge, Northwestern University; Smita Bhatia, University of Alabama at Birmingham; John Jefferies, University of Tennessee Health Science Center; Bonnie Ky, University of Pennsylvania; and Him Shrestha, Yue Pan, Qian Li, Kendrick Li, Stephanie Dixon, Matthew Erhardt, Daniel Mulrooney, Suiping Zhou, Haiyan Tan, Anthony High, Kirsten Ness, Melissa Hudson, Leslie Robinson, Gregory Armstrong, Junmin Peng and Yutaka Yasui, St . Jew.

The study was supported by grants from the National Cancer Institute of the National Institutes of Health (R01 CA261898, R01 CA216354, R21 CA261833, U24 CA55727, U01 CA195547, Cancer Center Support (CORE) Grant CA21765) and ALSAC, the fundraising and awareness organization St Jude.