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Cellular and Molecular Biology

Serum multiomics prediction of prognosis and adverse reactions to concurrent chemoradiotherapy in patients with esophageal cancer

British Journal of Cancer volume 133, pages 1829–1843 (2025)Cite this article

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Abstract

Objective

Concurrent chemoradiotherapy (CCRT) is an important treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). There is still a lack of reliable means to predict efficacy, prognosis and hematologic toxicity.

Design

We analyzed 127 serum samples before CCRT and 93 serum samples after CCRT from 127 ESCC patients via metabolomics by GC-MS. Combined with Olink proteomics, we constructed models to predict response and survival through machine learning. Multiple linear regression was used to construct hematologic toxicity prediction models. In combination with the proteomics of ESCC, metabolic changes were studied.

Results

A prediction model for the efficacy to CCRT was established via serum metabolomics and proteomics (Train, CR/nCR = 28/50, AUC = 0.9848, 95% CI = 0.9639–1.0000; Test, CR/nCR = 17/15, AUC = 0.8854, 95% CI = 0.7800–0.9908). A survival prediction model was established (n = 109, C-index = 0.7640, 95% CI = 0.7140–0.8140). Linear models for predicting hematologic toxicity were constructed (n = 111, R > 0.7). L-serine is important for the prognosis of patients with ESCC treated with CCRT, and SHMT2 is a key protein in serine metabolism that affects the efficacy of CCRT.

Conclusion

The combination of serum metabolomics with proteomics can effectively predict the prognosis and hematologic toxicity, which can provide important data for patients to choose treatment methods.

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Fig. 1
Fig. 2: Serum metabolomics and proteomics to predict CCRT efficacy.
Fig. 3: Serum metabolomics and proteomics predict the survival of ESCC patients receiving CCRT.
Fig. 4: Serum metabolites and proteins predict CCRT-induced hematologic toxicity.
Fig. 5: SHMT2 is a key protein in L-serine metabolism in ESCC.
Fig. 6: SHMT2 affects the sensitivity of ESCC cells to chemoradiotherapy.

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Data availability

The data for this study were extracted from published literature. Pertinent data are presented in both the manuscript and its Supplementary Material file.

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Acknowledgements

We are grateful to Professor Stanley Li Lin from Shantou University Medical College for assisting in proofreading and editing the manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (No. 82173034, No. 82273108), the Natural Science Foundation of China–Guangdong Joint Fund (No. U0932001 and No. U1301227), the Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province in 2021 (No. 210713116901849) and the Guangdong Innovative and Entrepreneurial Research Team Program (No. 2021KCXTD005).

Author information

Author notes

  1. These authors contributed equally: Wen-Zhi Wu, He-Cheng Huang, Guang-Hui Zhu.

Authors and Affiliations

  1. Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Department of Clinical Laboratory Medicine, Cancer Hospital, Shantou University Medical College, Shantou, 515041, Guangdong, China

    Wen-Zhi Wu, En-Min Li & Li-Yan Xu

  2. The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Institute of Oncologic Pathology, Department of Pathology, Second Affiliated Hospital, Shantou University Medical College, Shantou, 515041, Guangdong, China

    Wen-Zhi Wu, Lian-Di Liao, Man-Yu Chu, Shuai-Xia Yu, En-Min Li & Li-Yan Xu

  3. Shantou Central Hospital, Shantou, 515041, Guangdong, China

    He-Cheng Huang, Xu-Li Chen & Zhi-Mao Li

  4. Department of Forensic Medicine, Shantou University Medical College, Shantou, 515041, Guangdong, China

    Guang-Hui Zhu & Dian Wang

  5. Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, 515041, Guangdong, China

    En-Min Li

  6. Shantou Central Hospital, Shantou Academy Medical Sciences, Shantou, 515041, Guangdong, China

    En-Min Li

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Contributions

Conception and design: WZ, HH, GZ, and LX. Supervision: HH, EL, and LX. Development of methodology: WZ, GZ, ZL, MC, SY, and DW. Software: WZ. Formal analysis: WZ, and GZ. Acquisition of data: WZ, and LL. Data curation: WZ, HH, XC, ZL, MC, and SY. Visualization: WZ. Writing - original draft: WZ, HH, GZ, XC, and LX. Writing - review & editing: WZ, HH, EL, and LX. Resources: HH, GZ, LL, XC, ZL, MC, SY, and DW. Project administration: HH, and LX. Funding acquisition: HH, EL, and LX.

Corresponding authors

Correspondence to En-Min Li or Li-Yan Xu.

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Competing interests

The authors of this manuscript are not current editors or Editorial Board Member of British Journal of Cancer. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript.

Ethics approval and consent to participate

Patients with ESCC were selected from our nested cohort study registered on the Clinical Trial Management Public Platform, clinical registration number: ChiCTR180001624. Informed consent was obtained from the subject(s) and/or guardian(s). All participants were informed and voluntarily participated in this study and signed an informed consent form. The study was approved by the ethics committee of the Central Hospital of Shantou (2016--026, November 4, 2016), the Ethics Committee of Shantou University Medical College (SUMC-2021--15, March 14, 2021) and the Human Genetic Resources Committee of the Ministry of Science and Technology of China ([2021] CJ1260, [2022 BC0008]. The study was performed in accordance with the Declaration of Helsinki. Ethics related to animal experiments was not addressed in this study.

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Wu, WZ., Huang, HC., Zhu, GH. et al. Serum multiomics prediction of prognosis and adverse reactions to concurrent chemoradiotherapy in patients with esophageal cancer. Br J Cancer 133, 1829–1843 (2025). https://doi.org/10.1038/s41416-025-03229-5

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