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Serum metabolic traits reveal therapeutic toxicities and responses of neoadjuvant chemoradiotherapy in patients with rectal cancer

Author

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  • Hongmiao Wang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Huixun Jia

    (Shanghai Jiao Tong University School of Medicine
    Fudan University Shanghai Cancer Center)

  • Yang Gao

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Haosong Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Jin Fan

    (Fudan University Shanghai Cancer Center)

  • Lijie Zhang

    (Fudan University Shanghai Cancer Center)

  • Fandong Ren

    (Chinese Academy of Sciences)

  • Yandong Yin

    (Chinese Academy of Sciences)

  • Yuping Cai

    (Chinese Academy of Sciences)

  • Ji Zhu

    (Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)
    Chinese Academy of Sciences
    Zhejiang Key Laboratory of Radiation Oncology
    Fudan University Shanghai Cancer Center)

  • Zheng-Jiang Zhu

    (Chinese Academy of Sciences
    Shanghai Key Laboratory of Aging Studies)

Abstract

Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for patients with locally advanced rectal cancer (LARC). Therapeutic efficacy of nCRT is significantly affected by treatment-induced diarrhea and hematologic toxicities. Metabolic alternations in cancer therapy are key determinants to therapeutic toxicities and responses, but exploration in large-scale clinical studies remains limited. Here, we analyze 743 serum samples from 165 LARC patients recruited in a phase III clinical study using untargeted metabolomics and identify responsive metabolic traits over the course of nCRT. Pre-therapeutic serum metabolites successfully predict the chances of diarrhea and hematologic toxicities during nCRT. Particularly, levels of acyl carnitines are linked to sex disparity in nCRT-induced diarrhea. Finally, we show that differences in phenylalanine metabolism and essential amino acid metabolism may underlie distinct therapeutic responses of nCRT. This study illustrates the metabolic dynamics over the course of nCRT and provides potential to guide personalized nCRT treatment using responsive metabolic traits.

Suggested Citation

  • Hongmiao Wang & Huixun Jia & Yang Gao & Haosong Zhang & Jin Fan & Lijie Zhang & Fandong Ren & Yandong Yin & Yuping Cai & Ji Zhu & Zheng-Jiang Zhu, 2022. "Serum metabolic traits reveal therapeutic toxicities and responses of neoadjuvant chemoradiotherapy in patients with rectal cancer," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35511-y
    DOI: 10.1038/s41467-022-35511-y
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    References listed on IDEAS

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    1. Dylan Dodd & Matthew H. Spitzer & William Van Treuren & Bryan D. Merrill & Andrew J. Hryckowian & Steven K. Higginbottom & Anthony Le & Tina M. Cowan & Garry P. Nolan & Michael A. Fischbach & Justin L, 2017. "A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites," Nature, Nature, vol. 551(7682), pages 648-652, November.
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