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Common alterations in plasma free amino acid profiles and gut microbiota-derived tryptophan metabolites of five types of cancer patients

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Abstract

Amino acids not only play a vital role in the synthesis of biological molecules such as proteins in cancer malignant cells, they are also essential metabolites for immune cell activation and antitumor effects in the tumor microenvironment. The abnormal changes in amino acid metabolism are closely related to the occurrence and development of tumors and immunity. Intestinal microorganisms play an essential role in amino acid metabolism, and tryptophan and its intestinal microbial metabolites are typical representatives. However, it is known that the cyclic amino acid profile is affected by specific cancer types, so relevant studies mainly focus on one type of cancer and rarely study different cancer forms at the same time. The objective of this study was to examine the PFAA profile of five cancer patients and the characteristics of tryptophan intestinal microbial metabolites to determine whether there are general amino acid changes across tumors. Plasma samples were collected from esophageal (n = 53), lung (n = 73), colorectal (n = 94), gastric (n = 55), breast cancer (n = 25), and healthy control (HC) (n = 139) subjects. PFAA profile and tryptophan metabolites were measured, and their perioperative changes were examined using high-performance liquid chromatography. Univariate analysis revealed significant differences between cancer patients and HC. Furthermore, multivariate analysis discriminated cancer patients from HC. Regression diagnosis models were established for each cancer group using differential amino acids from univariate analysis. Receiver-operating characteristic analysis was applied to evaluate these diagnosis models. Finally, GABA, arginine, tryptophan, taurine, glutamic acid, and melatonin showed common alterations across all types of cancer patients. Metabolic pathway analysis shows that the most significant enrichment pathways were tryptophan, arginine, and proline metabolism. This study provides evidence that common alterations of the metabolites mentioned above suggest their role in the pathogenesis of each cancer patient. It was suggested that multivariate models based on PFAA profiles and tryptophan metabolites might be applicable in the screening of cancer patients.

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Data availability

The data that support the findings of the current study are available on reasonable request from the corresponding author. The data are not publicly available due to restrictions e.g. containing information that could compromise the privacy of research participants.

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Acknowledgements

The authors acknowledge the support of Gulou Hospital and Southeast University, Nan**g, China.

Funding

This study was funded by the National Science Foundation of China (No. 82173575), the Fundamental Research Funds for the Central Universities (2242021k30014), and the Fundamental Research Funds for the Central Universities (2242021k30059).

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Author notes

  1. Ahad Hussain and Li **e are joint co-first authors.

Authors and Affiliations

  1. Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nan**g, 210009, China

    Ahad Hussain & Xuejun Kang

  2. College of Animal Science and Food Engineering, **ling Institute of Technology, Nan**g, 210038, Jiangsu, China

    Li **e

  3. Key Laboratory of Child Development and Learning Science of Ministry of Education of China, School of Biological Sciences and Medical Engineering, Southeast University, Nan**g, 210096, China

    Ahad Hussain, Guozhe Deng & Xuejun Kang

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  1. Ahad Hussain
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  2. Li **e
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Contributions

Ahad Hussain, First author, wrote the main manuscript text and statistical analysis Li **e. Equal contribution, method development and manuscript revision Guozhe Dengc. Experimental method development Xuejun Kang. Corresponding author, conceptualization, manuscript revision.

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Correspondence to Xuejun Kang.

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Hussain, A., **e, L., Deng, G. et al. Common alterations in plasma free amino acid profiles and gut microbiota-derived tryptophan metabolites of five types of cancer patients. Amino Acids 55, 1189–1200 (2023). https://doi.org/10.1007/s00726-023-03308-y

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