Untargeted metabolomics analysis of metabolite changes in gastric cancer patients from plateau regions

doi:10.4251/wjgo.v17.i9.109777

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastrointest Oncol. Sep 15, 2025; 17(9): 109777
Published online Sep 15, 2025. doi: 10.4251/wjgo.v17.i9.109777

Untargeted metabolomics analysis of metabolite changes in gastric cancer patients from plateau regions

Ling-Hong Zhu, Zhao-Xin Jin, Yan-Qing Ma, Xiao Feng, Cai-Hong Ci, Yun-Song Zhou, Qiao-Ling Gu, Yong-Mei Lan, Zi-Long Zhang

Ling-Hong Zhu, Yan-Qing Ma, Xiao Feng, Cai-Hong Ci, Yun-Song Zhou, Qiao-Ling Gu, Department of Science and Education, Northwest Minzu University, Lanzhou 730030, Gansu Province, China

Zhao-Xin Jin, Department of Emergency, The Fourth People's Hospital of Qinghai Province, Xining 810001, Qinghai Province, China

Yong-Mei Lan, Department of Gastrointestinology, Northwest Minzu University, Lanzhou 730030, Gansu Province, China

Zi-Long Zhang, Department of Oncosurgery, Qinghai Provincial People's Hospital, Xining 810007, Qinghai Province, China

Co-first authors: Ling-Hong Zhu and Zhao-Xin Jin.

Co-corresponding authors: Yong-Mei Lan and Zi-Long Zhang.

Author contributions: Zhu LH and Jin ZX, as co-first authors, made equal contributions to this work. The designation of Zhu LH and Jin ZX as co-first authors serve three key purposes. First, this collaborative research project accurately reflects the division of responsibilities and workload during its completion and paper writing. This arrangement ensures effective communication and post-submission management, ultimately enhancing the quality and reliability of the research. Second, the research team comprises authors from diverse disciplines with specialized expertise, and the co-first authorship best demonstrates this diversity. This structure facilitates comprehensive and in-depth exploration of the research topic, enriching readers 'understanding through multiple expert perspectives. Third, both researchers contributed equally throughout the research process. By selecting these scholars as co-first authors, we acknowledge their equal contributions while recognizing the team's collaborative spirit. In conclusion, we consider the designation of Zhu LH and Jin ZX as co-first authors appropriate, as it accurately reflects our team's collaborative ethos, balanced contributions, and diversity. Lan YM and Zhang ZL contribute equally to this study as co-corresponding authors. They made critical revisions to the important intellectual content of the manuscript, and played a role in designing the work, preparing, validating and supervising the manuscript, and participating in the revision process. Zhu LH, Jin ZX, Ma YQ, Feng X, Ci CH, Zhou YS, Gu QL, Lan YM, and Zhang ZL were responsible for research design; Ma YQ, Feng X, and Ci CH conducted laboratory testing and clinical data collection; Zhou YS and Gu QL performed tool analysis; Zhu LH and Jin ZX handled data analysis and co-authored the paper; Lan YM and Zhang ZL provided critical revisions to the manuscript's intellectual content, participated in the work design, manuscript preparation, validation, supervision, and revision processes; all authors have reviewed and approved the final version.

Supported by Gansu Provincial Natural Science Foundation Project, No. 23JRRA725; Postgraduate Research Innovation Project of Northwest Minzu University in 2025, No. 31920250001-38; and 2024 Qinghai Province's "Kunlun Talent High-end Innovative and Entrepreneurial Talent Project" Cultivates Top Talents Project, No. QHKLYC-GDCXCY-2024-155.

Institutional review board statement: The study was reviewed and approved by the Qinghai Provincial People's Hospital Institutional Review Board.

Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.

Conflict-of-interest statement: The authors declare no conflict of interest in relation to this study.

STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.

Data sharing statement: Not available.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Yong-Mei Lan, MD, Professor, Department of Gastrointestinology, Northwest Minzu University, No. 1 Northwest New Village, Lanzhou 730030, Gansu Province, China. xbmdlym@sina.com

Received: May 27, 2025
Revised: June 9, 2025
Accepted: August 19, 2025
Published online: September 15, 2025
Processing time: 116 Days and 10.4 Hours

Abstract

BACKGROUND

Metabolomics sequencing technology was used to investigate the changes of intestinal flora and metabolites in gastric cancer patients in plateau areas.

AIM

To investigate changes in gut microbiota and their metabolites in patients with gastric cancer from plateau regions using untargeted metabolomic sequencing.

METHODS

Fresh morning fecal samples were collected from 30 gastric cancer patients diagnosed at a tertiary hospital in Qinghai Province and 30 healthy individuals (controls). Liquid chromatography-tandem mass spectrometry based untargeted metabolomic sequencing was used to analyze metabolite changes and predict metabolic function.

RESULTS

Metabolomic analysis identified 281 metabolites in samples from both groups. These metabolites were categorized into eight major classes, listed in descending order of abundance: Lipids and lipid-like molecules (35.443%); organic acids and derivatives (29.114%); organic oxygen compounds (15.19%); nucleosides, nucleotides, and analogs (13.924%); organoheterocyclic compounds (2.532%), amino acids and peptides (1.266%); benzenoids (1.266%); and fatty acids (1.266%). Compared with the control group, the top 10 metabolites elevated in the gastric cancer group included: Dethiobiotin, glycylproline, glycine, hydroxyisocaproic acid, tyramine, methionine sulfoxide, 5-aminopentanoic acid, citrulline, betonicine, and formiminoglutamic acid and the top 10 decreased were: Cytidine, 5'-methylthioadenosine, trehalose, melibiose, lotaustralin, adenosine, inosine, ribothymidine, raffinose, and galactinol. Functional prediction analysis revealed that these differential metabolites were primarily enriched in 12 metabolic pathways, including purine metabolism, cysteine and methionine metabolism, galactose metabolism, lysine degradation, glycine, serine, and threonine metabolism, biotin metabolism, pyrimidine metabolism, arginine and proline metabolism, histidine metabolism, primary bile acid biosynthesis, starch and sucrose metabolism, and tyrosine metabolism.

CONCLUSION

Significant differences in intestinal microbial metabolites and associated metabolic pathways were observed between gastric cancer patients and healthy controls residing in plateau regions.

Keywords: Plateau regions; Gastric cancer; Untargeted metabolomics; Metabolites; Metabolic pathways

Core Tip: This study reveals distinct alterations in gut microbial metabolites and metabolic pathways in gastric cancer patients from high-altitude regions, highlighting potential metabolic biomarkers and pathways (e.g., purine, biotin, and amino acid metabolism) that may inform early diagnosis or targeted therapies in this unique population.