Using data from the St. Jude Lifetime Cohort (St. Jude LIFE), Yadav Sapkota, PhD, St. Jude Department of Epidemiology and Cancer Control, designed a 27-protein model capable of accurately estimating treatment-related cardiomyopathy risk in pediatric cancer survivors.
Early disease detection is beneficial for securing the best possible outcomes for patients. But finding noninvasive, effective ways to predict disease risk is a tremendous challenge. Findings from scientists at St. Jude Children’s Research Hospital are showing promise for assessing cardiomyopathy risk in childhood cancer survivors. Heart disease is a well-established late effect for pediatric cancer survivors treated with anthracycline chemotherapy. The researchers identified a panel of 27 proteins as biomarkers of cardiomyopathy risk when 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 and half without cardiomyopathy. The findings were published today in JACC: CardioOncology.
While highly effective for the treatment of solid and hematological pediatric cancers, anthracycline chemotherapy drugs such as doxorubicin are well-known to increase the risk of cardiomyopathy — heart muscle disease. Patients who receive anthracycline treatment can expect a two-to-five-time higher chance of developing heart disease with five-year survival rates of less than 50% after diagnosis. Current methods used to assess cardiomyopathy risk in survivors, such as routine echocardiograms, are less effective for early detection, with diagnosis usually occurring past the point of curative treatment.
Recognizing the need for an accurate and affordable prediction tool for cardiomyopathy, Yadav Sapkota, PhD, St. Jude Department of Epidemiology & Cancer Control, sought to leverage the routine blood test. “We already measure proteins in regular lab tests, so this test, using circulating biomarkers, can be done as easily — a simple blood sample is all that’s needed.”
“The goal is to more accurately identify asymptomatic people who are more likely to develop cardiomyopathy as they become survivors of childhood cancer and then grow into adulthood,” he added.
A robust panel to detect preclinical cardiomyopathy
Sapkota’s team examined participants of the St. Jude LIFE cohort. This ongoing study aims to comprehensively document the lifetime impact of pediatric cancer through retrospective and prospective data collection and analysis. The researchers matched 98 survivors with cardiomyopathy with a comparable cardiomyopathy-free group.
The goal was to identify “subclinical” cases of cardiomyopathy before symptoms arise. “Seventy-five of our samples presented with cardiomyopathy, but they didn’t have symptoms — what we call subclinical based on reduced heart function,” Sapkota explained. “We looked into over 800 proteins in those patients who didn’t have symptoms yet, and we found 27 proteins that were differentially expressed in that group.”
The team investigated if this subset of proteins could be used to predict the risk of severe disease in an independent sample of survivors. “If we can use those proteins to predict who is likely to develop severe outcomes, we can then go back to asymptomatic patients or even those who don’t have any reduced cardiac function and make a prediction if this person is likely to develop severe outcome down the road.”
Based on the pilot study, the expansion of the research is ongoing. “The plan is to assess circulating biomarkers for everybody in St. Jude LIFE — almost 5,000 individuals,” Sapkota said. “And while cardiomyopathy is something we started on, we aim to evaluate other outcomes, such as diabetes, second cancers and many others. It’s going to be a great resource.”
Authors and funding
The study’s first author 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. Jude.
The study was supported by grants from the National Cancer Institute at 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 of St. Jude.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer, sickle cell disease, and other life-threatening disorders. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 60 years ago. St. Jude shares the breakthroughs it makes to help doctors and researchers at local hospitals and cancer centers around the world improve the quality of treatment and care for even more children. To learn more, visit stjude.org, read St. Jude Progress, a digital magazine, and follow St. Jude on social media at @stjuderesearch.