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Investigators from the UH John A. Burns School of Medicine and UH Cancer Center make impactful discovery
Researchers at the University of Hawaiʻi have identified a panel of 31 small non-coding RNAs (sncRNAs) in circulating plasma exosomes associated with lung cancer risk up to 10 years before clinical diagnosis. The findings suggest the potential for a blood-based approach to identify individuals at elevated risk during the preclinical period, when lung cancer may be developing but remains clinically undetected.
The study was led by corresponding author Youping Deng, PhD, first author and PhD candidate Zhuokun Feng, MD, and second author Masaki Nasu, PhD, from the Department of Quantitative Health Sciences at the University of Hawaiʻi at Mānoa John A. Burns School of Medicine. Deng is also a researcher at the University of Hawaiʻi Cancer Center’s Cancer Biology program as well as co-director of the UH Cancer Center’s Genomics and Bioinformatics Shared Resource. Loïc Le Marchand, MD, PhD, also of the UH Cancer Center, and the contact PI of the Multiethnic Cohort (MEC) Study, served as a co-corresponding author.
The article, A Panel of Circulating Exosomal sncRNAs Associated with Lung Cancer Risk up to 10 Years in Advance, has been published in Advanced Science and is available at: https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.76729
Using pre-diagnostic plasma samples from the Multiethnic Cohort (MEC), the researchers identified a 31-sncRNA signature consisting of 15 microRNAs, eight PIWI-interacting RNAs, seven tRNA-derived fragments, and one tRNA half.
A random forest classifier based on this signature achieved an AUC of 0.97, with 93% sensitivity, 100% specificity, and 95% overall accuracy in held-out testing. The sncRNA-derived risk score remained strongly associated with subsequent lung cancer after adjustment for age, sex, ethnicity, smoking intensity, and smoking duration, indicating that the signature captured predictive information beyond conventional demographic and smoking-related factors.
Importantly, the association remained detectable during the five-to-ten-year period before clinical diagnosis, suggesting that circulating exosomal sncRNAs may reflect early biological changes associated with lung carcinogenesis well before a tumor becomes clinically apparent.
“A central question in this study was whether a molecular signal of future lung cancer could already be present in blood many years before diagnosis,” said Zhuokun Feng, MD, the study’s first author.
“Our goal was not simply to distinguish patients with established lung cancer from cancer-free individuals, but to identify molecular signals that may indicate high lung cancer risk years before clinical diagnosis,” said Youping Deng, PhD, senior and corresponding author of the study.
Together, these findings highlight the potential of the 31-sncRNA signature as a blood-based tool for long-term lung cancer risk assessment. The research team is pursuing patent protection for the biomarker panel and its potential clinical application.
This project was supported by grants from the National Institutes of Health (U54MD007601, R01CA223490, 1UE5HG013826, and U01CA164973).
Feng Z, Nasu M, Abdul-Ghani A, Chen Y, Chen S, Ibrahim IM, Zhang H, Higa L, Gao Z, Yang H, Bueno R, Marchand LL, Deng Y. A Panel of Circulating Exosomal sncRNAs Associated With Lung Cancer Risk up to 10 Years in Advance. Adv Sci (Weinh). 2026 Aug 14. doi: 10.1002/advs.76729. PMID: 42596913; PMCID: PMC13474057.
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The University of Hawaiʻi Cancer Center is dedicated to saving lives in Hawaiʻi and the Pacific, and inspiring hope by working to conquer cancer. The flagship priority is to understand and address cancer health disparities. The center strives to achieve this through research, education, patient care, and community outreach, focusing on the unique and diverse ethnic, cultural, and environmental characteristics of Hawaiʻi and the Pacific.
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