Modifications of microbiome-derived cell-free RNA in plasma discriminates colorectal cancer samples

Cheng-Wei Ju^{1

2

3}, Ruitu Lyu^{1

2}, Han Li^{1

2}, Jiangbo Wei^{1

2}, Alberto J Parra Vitela⁴, Urszula Dougherty⁵, Akushika Kwesi⁵, Alexander Luna⁵, Xuanhao Zhu^{1

2}, Shenghai Shen^{6

7}, Yunzheng Liu⁸, Liangliang Wang⁹, Xiaolong Cui^{1

2}, Yuzhi Xu¹⁰, Bochen Jiang^{1

2}, Yiyi Ji^{1

2}, Peng Xia^{1

2}, Diana C West-Szymanski^{1

2}, Chenxi Sun^{1

2}, Yuhao Zhong^{1

2}, Chang Ye^{1

2}, Angelica Moran¹¹, Christopher Lehmann⁵, Eric Pamer⁵, Wei Zhang¹², Marc Bissonnette¹³, Li-Sheng Zhang^{14

15}, Chuan He^{16

17

18}

Affiliations

¹ Department of Chemistry, The University of Chicago, Chicago, IL, USA.
² Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, USA.
³ Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL, USA.
⁴ Colon and Rectal Surgery, Advocate Lutheran General Hospital, Park Ridge, IL, USA.
⁵ Department of Medicine, The University of Chicago, Chicago, IL, USA.
⁶ Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.
⁷ Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong, China.
⁸ Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
⁹ The Laboratory of Microbiome and Microecological Technology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
¹⁰ Department of Chemistry, New York University, New York, NY, USA.
¹¹ Department of Pathology, The University of Chicago, Chicago, IL, USA.
¹² Department of Preventive Medicine and The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹³ Department of Medicine, The University of Chicago, Chicago, IL, USA. mbissonn@bsd.uchicago.edu.
¹⁴ Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China. zhangls@ust.hk.
¹⁵ Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong, China. zhangls@ust.hk.
¹⁶ Department of Chemistry, The University of Chicago, Chicago, IL, USA. chuanhe@uchicago.edu.
¹⁷ Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, USA. chuanhe@uchicago.edu.
¹⁸ Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL, USA. chuanhe@uchicago.edu.

PMID: 40629040
DOI: 10.1038/s41587-025-02731-8

Modifications of microbiome-derived cell-free RNA in plasma discriminates colorectal cancer samples

Cheng-Wei Ju et al. Nat Biotechnol. 2025.

. 2025 Jul 8.

doi: 10.1038/s41587-025-02731-8. Online ahead of print.

Authors

Affiliations

¹ Department of Chemistry, The University of Chicago, Chicago, IL, USA.
² Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, USA.
³ Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL, USA.
⁴ Colon and Rectal Surgery, Advocate Lutheran General Hospital, Park Ridge, IL, USA.
⁵ Department of Medicine, The University of Chicago, Chicago, IL, USA.
⁶ Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.
⁷ Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong, China.
⁸ Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
⁹ The Laboratory of Microbiome and Microecological Technology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
¹⁰ Department of Chemistry, New York University, New York, NY, USA.
¹¹ Department of Pathology, The University of Chicago, Chicago, IL, USA.
¹² Department of Preventive Medicine and The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹³ Department of Medicine, The University of Chicago, Chicago, IL, USA. mbissonn@bsd.uchicago.edu.
¹⁴ Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China. zhangls@ust.hk.
¹⁵ Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong, China. zhangls@ust.hk.
¹⁶ Department of Chemistry, The University of Chicago, Chicago, IL, USA. chuanhe@uchicago.edu.
¹⁷ Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, USA. chuanhe@uchicago.edu.
¹⁸ Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL, USA. chuanhe@uchicago.edu.

PMID: 40629040
DOI: 10.1038/s41587-025-02731-8

Abstract

Circulating cell-free RNA (cfRNA) in plasma represents a promising avenue for cancer detection. We report low-input multiple methylation sequencing, a method for profiling modification patterns in cfRNA, enabling the detection of diverse transfer RNAs and small noncoding RNAs derived from both the human genome and the microbiome. RNA modification patterns in microbiome-derived cfRNA accurately reflect host microbiota activity and hold potential for the early detection of colorectal cancer.

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Conflict of interest statement

Competing interests: A patent application for LIME-seq and cfRNA modification as biomarkers has been filed by the University of Chicago. C.H. is a scientific founder, member of the scientific advisory board and equity holder of Aferna Bio, Ellis Bio and AllyRNA, a scientific cofounder and equity holder of Accent Therapeutics and a member of the scientific advisory board of Rona Therapeutics. The remaining authors declare no competing interests.

References

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Modifications of microbiome-derived cell-free RNA in plasma discriminates colorectal cancer samples

Affiliations

Modifications of microbiome-derived cell-free RNA in plasma discriminates colorectal cancer samples

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

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