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DNA remnants in red blood cells enable early detection of cancer

Haobo Sun^1,2,3,4,† , Xingyun Yao^2,3,4,5,† , Yurong Jiao⁶ , Xiangxing Kong⁶ , Yuehua Han⁷ , Ying Li² , Jianping Ge² , Yanfei Cao⁸ , Hongsheng Lu⁹ , Pingli Wang¹⁰ , Yu Xu¹¹ , Jun Li⁶ , Kefeng Ding⁶ , Xiaofei Gao^2,3,4,*

¹School of Basic Medical Science, Fudan University, Shanghai, China
²Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
³Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China
⁴Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
⁵College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China
⁶Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
⁷Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
⁸Department of Gastroenterology, Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
⁹Department of Pathology, Taizhou Central Hospital Taizhou University Hospital, Taizhou, Zhejiang, China
¹⁰Department of Respiratory Medicine, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang, China
¹¹Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
^†These authors contributed equally: Haobo Sun, Xingyun Yao
* Correspondence: Xiaofei Gao(gaoxiaofei@westlake.edu.cn)

Cytoplasmic DNA emerges as a consequence of genomic instability. However, its potential role in disease diagnosis has yet to be fully explored. Here we analyzed DNA remnants in mature red blood cells (rbcDNA) from both healthy individuals and cancer patients. Our study unveiled distinct genomic profiles in rbcDNA from cancer patients with early-stage solid tumors compared to those of healthy donors. Significant changes in read counts at specific genomic regions within rbcDNA were identified in patients, which were termed tumor-associated rbcDNA features. These features demonstrated potential for highly accurate early-stage cancer detection, proposing a novel approach for cancer detection. Moreover, tumor-associated rbcDNA features were observed in tumor mouse models, with some features being conserved between mice and humans. Chronic, but not transient, up-regulation of interleukin-18 is essential for the development of these features by promoting DNA damage in bone marrow hematopoietic cells through the up-regulation of NR4A1. These results underscore the remote regulation of chromosomal stability in hematopoietic cells by solid tumors and propose tumor-associated rbcDNA features as a promising strategy for early cancer detection.

https://doi.org/10.1038/s41422-025-01122-7

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