Serum metabolomics analysis of biomarkers and metabolic pathways in patients with colorectal cancer associated with spleen-deficiency and qi-stagnation syndrome or damp-heat syndrome: a prospective cohort study

Min Zou; Yan-Sheng Zhang; Jin-Kai Feng; Hao Tu; Ming-Bin Gui; Ya-Nan Wang; Zi-Jie Yang; Zeng-Qiang Yang; Ming Xu; Wei-Qiang Wu; Feng Gao

doi:10.3389/fonc.2023.1190706

Serum metabolomics analysis of biomarkers and metabolic pathways in patients with colorectal cancer associated with spleen-deficiency and qi-stagnation syndrome or damp-heat syndrome: a prospective cohort study

Front Oncol. 2023 Sep 12:13:1190706. doi: 10.3389/fonc.2023.1190706. eCollection 2023.

Authors

Min Zou¹, Yan-Sheng Zhang², Jin-Kai Feng³, Hao Tu⁴, Ming-Bin Gui¹, Ya-Nan Wang¹, Zi-Jie Yang¹, Zeng-Qiang Yang⁵, Ming Xu¹, Wei-Qiang Wu¹, Feng Gao¹

Affiliations

¹ Department of Colorectal and Anal Surgery, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou, China.
² Department of Obstetrics and Gynecology, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, China.
³ Department of Hepatic Surgery VI, The Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, China.
⁴ Department of Colorectal Surgery, Chongqing Qijiang District People's Hospital, Chongqing, China.
⁵ Department of Colorectal Surgery, Gansu Provincial Central Hospital, Lanzhou, China.

Abstract

Objective: To profile the serum metabolites and metabolic pathways in colorectal cancer (CRC) patients associated with spleen-deficiency and qi-stagnation syndrome (SDQSS) or damp-heat syndrome (DHS).

Methods: From May 2020 to January 2021, CRC patients diagnosed with traditional Chinese medicine (TCM) syndromes of SDQSS or DHS were enrolled. The clinicopathological data of the SDQSS and DHS groups were compared. The serum samples were analyzed by liquid chromatography-mass spectrometry (LC-MS). The variable importance in the projection >1, fold change ≥3 or ≤0.333, and P value ≤0.05 were used to identify differential metabolites between the two groups. Furthermore, areas under the receiver operating characteristic (ROC) curve > 0.9 were applied to select biomarkers with good predictive performance. The enrichment metabolic pathways were searched through the database of Kyoto Encyclopedia of Genes and Genomes.

Results: 60 CRC patients were included (30 SDQSS and 30 DHS). The level of alanine aminotransferase was marginally significantly higher in the DHS group than the SDQSS group (P = 0.051). The other baseline clinicopathological characteristics were all comparable between the two groups. 23 differential serum metabolites were identified, among which 16 were significantly up-regulated and 7 were significantly down-regulated in the SDQSS group compared with the DHS group. ROC curve analysis showed that (S)-3-methyl-2-oxopentanoic acid, neocembrene, 1-aminocyclopropanecarboxylic acid, 3-methyl-3-hydroxypentanedioate, and nicotine were symbolic differential metabolites with higher predictive power. The top five enrichment signalling pathways were valine, leucine and isoleucine biosynthesis; lysosome; nicotine addiction; fructose and mannose metabolism; and pertussis.

Conclusion: Our study identifies the differential metabolites and characteristic metabolic pathways among CRC patients with SDQSS or DHS, offering the possibility of accurate and objective syndrome differentiation and TCM treatment for CRC patients.

Keywords: colorectal cancer (CRC); damp-heat syndrome (DHS); liquid chromatography-mass spectrometry (LC-MS); metabolomics; spleen-deficiency and qi-stagnation syndrome (SDQSS).

Grants and funding

This work was supported by Natural Science Foundation of Gansu Province (20YF8FA098), the Fundamental Research Funds for the Central Universities of Northwest Minzu University (331920200016), and Science and Technology Planning Project of Gansu Province (23JRRA539).