Early disease detection is beneficial in ensuring the best possible outcomes for patients. But finding non-invasive, effective ways to predict disease risk is a huge challenge. Findings from scientists at St. Jude Children’s Research Hospital show promise for research cardiomyopathy risk in childhood cancer survivors. Heart disease is a known late effect in childhood cancer survivors treated with anthracycline chemotherapy. The researchers identified a panel of 27 proteins as biomarkers for the risk of cardiomyopathy, 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: Cardio-Oncology.
Although highly effective for treating solid and hematologic childhood cancers, anthracycline chemotherapy drugs such as doxorubicin are known to increase the risk of cardiomyopathy; myocardial disease. Patients receiving anthracycline treatment can expect to be two to five times more likely to develop heart disease, with five-year survival rates of less than 50% after diagnosis. Current methods used to assess the risk of cardiomyopathy in survivors, such as routine echocardiograms, are less effective for early detection, with diagnosis usually occurring beyond the point of curative treatment.
Yadav Sapkota, PhD, St. Jude Department of Epidemiology & Cancer Control, realizing the need for an accurate and affordable cardiomyopathy prediction tool, sought to utilize the routine blood test. “We already measure proteins in regular laboratory tests, so this test, using circulating biomarkers, 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 become childhood cancer survivors and then grow into adulthood.”
Yadav Sapkota, PhD, St. Jude Department of Epidemiology and Cancer Control
A robust panel to detect preclinical cardiomyopathy
Sapkota’s team examined participants from the St. Jude LIFE cohort. This ongoing study aims to comprehensively document the lifetime impact of childhood cancer through retrospective and prospective data collection and analysis. The researchers matched 98 survivors with cardiomyopathy with a comparable cardiomyopathy-free group.
The aim was to identify ‘subclinical’ cases of cardiomyopathy before symptoms appear. “Seventy-five of our samples showed cardiomyopathy, but they had no symptoms; what we call subclinical, based on impaired cardiac function,” Sapkota explained. “We examined more than 800 proteins in patients who did not yet have symptoms, and we found 27 proteins that were differentially expressed in that group.”
The team investigated 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 those proteins to predict who is likely to develop serious outcomes, we can go back to asymptomatic patients or even those who do not have any impaired cardiac function and make a prediction as to whether this person is likely to develop a serious outcome.” on the road.”
Based on the pilot study, the expansion of the research will continue. “The plan is to assess circulating biomarkers for everyone in St. Jude LIFE – nearly 5,000 individuals,” Sapkota said. “And while cardiomyopathy is something we’ve started with, we also want to evaluate other outcomes such as diabetes, second cancers and many others. It will be a great resource.”
Authors and funding
The study’s lead 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 Judas.
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 Fund. organization of St. Jude.
Source:
Magazine reference:
Poudel, S., et al. (2024) Serum proteins predict treatment-related cardiomyopathy in childhood cancer survivors. JACC: Cardio-Oncology. doi.org/10.1016/j.jaccao.2024.10.004.
