Journal of Traditional Chinese Medicine >
Integrated analysis of plasma metabolomics and proteomics reveals the biological characteristics of damp-heat and stasis-toxin syndrome in colorectal cancer
Received date: 2025-02-11
Accepted date: 2025-08-25
Online published: 2025-12-04
Supported by
key project of the National Natural Science Foundation of China: Biological Basis of Core Pathogenesis Syndrome in Colorectal Cancer Liver Metastasis and the Mechanism of Action of Xianlian Jiedu Decoction in Prevention and Treatment(82430122);National Key R&D Program of China: Research on Cancer Toxicity Pathogenesis Theory and Its Guidance for Prevention and Treatment Strategies of Malignant Tumors(2022YFC3500200);National Key R&D Program of China: Research on Cancer Toxicity Pathogenesis Theory and Its Guidance for Prevention and Treatment Strategies of Malignant Tumors(2022YFC3500202);Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine: Inheritance and Innovation Team for Cancer Toxin Pathogenesis Theory in Prevention and Treatment of Gastrointestinal Malignancies(ZYYCXTD-C-202208)
OBJECTIVE: To investigate the biological attributes of core syndromes in colorectal cancer, namely, the damp-heat and stasis-toxin syndrome (SRYD).
METHODS: Between October 2021 and October 2022, a cohort comprising 40 patients with colorectal cancer (CRC) diagnosed with damp-heat and stasis-toxin syndrome (SRYD group), 40 patients with CRC without this syndrome (non-SRYD group), and 40 healthy controls (Normal group) was recruited at Jiangsu Province Hospital of Chinese Medicine. Untargeted metabolomics analysis was conducted on plasma samples from all 120 participants, while differential protein analysis using four-dimensional data-independent acquisition proteomics was performed on 20 randomly selected samples per group. A combined analysis of proteomics and metabolomics data followed, and the identified potential diagnostic biomarkers were subsequently used to train and validate multiple machine learning models.
RESULTS: Proteomic analysis revealed 130 differential proteins in the colorectal cancer with damp-heat and stasis-toxin syndrome (CRC-SRYD) group, enriched in pathways including complement and coagulation cascades, as well as nuclear factor kappa-B (NF-κB) signaling. Metabolomic analysis identified 584 differential metabolites within the same group, showing enrichment in pathways such as primary bile acid biosynthesis, central carbon metabolism in cancer, and glucagon signaling. Integrated pathway analysis indicated heightened activity of the NF-κB signaling pathway in the CRC-SRYD group. A biomarker panel, comprising 6 proteins and 9 metabolites selected through the ReliefF algorithm, was used to construct a diagnostic model with random forest, achieving an accuracy of 93.33%, sensitivity of 80.00%, and specificity of 100%.
CONCLUSION: This study systematically elucidates plasma metabolomic and proteomic alterations in patients with CRC, establishing a robust diagnostic model for CRC syndrome (CRC-SRYD). Further investigation is warranted to clarify the underlying molecular mechanisms and biological foundations.
QIAN Jingyang , ZHANG Qinchang , ZHANG Dong , SHI Heweng , GENG Xuechen , SUN Xiaohe , SUN Dongdong , CHENG Haibo . Integrated analysis of plasma metabolomics and proteomics reveals the biological characteristics of damp-heat and stasis-toxin syndrome in colorectal cancer[J]. Journal of Traditional Chinese Medicine, 2026 , 46(3) : 695 -705 . DOI: 10.19852/j.cnki.jtcm.20251204.001
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