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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1433219
This article is part of the Research Topic Targeted Immunometabolic Therapy for Tumors View all 4 articles

The relationship between metabolite mediated immune regulatory imbalance and the occurrence of malignant tumors of bone and articular cartilage: A Mendelian randomization study

Provisionally accepted
Kehan Long Kehan Long 1Ao Gong Ao Gong 2Tengfei Zheng Tengfei Zheng 3*Shoushen Liu Shoushen Liu 3Zhendong Ying Zhendong Ying 2*Cong Xiao Cong Xiao 1*
  • 1 Mianyang Third People's Hospital, Mianyang, China
  • 2 Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
  • 3 Shandong First Medical University, Tai'an, Shandong, China

The final, formatted version of the article will be published soon.

    Background: This study aims to assess the causal relationship between immune cell characteristics and malignant tumors of bone and articular cartilage, focusing on the mediating role of metabolites.Using Mendelian randomization, we evaluated these relationships based on genetic variations to identify potential biomarkers and therapeutic targets.Methods: A two-sample Mendelian randomization analysis was conducted using GWAS data for immune cell features and 1,400 metabolites to investigate direct and mediating effects. Effective instrumental variables (IVs) were selected, and statistical analyses-including inverse variance weighting (IVW), weighted median, and mode-based methods-were performed using R software.This approach enabled the assessment of direct causal relationships as well as the potential mediating role of metabolites in the association between immune cell features and malignancies.Results: Significant causal relationships were identified between 26 immune phenotypes and the risk of malignant tumors of bone and articular cartilage. Notably, the HLA DR+ NK cell phenotype SSC-A showed a positive correlation with the risk of these malignancies. Further analysis revealed causal relationships with 67 metabolites, 38 of which were positively correlated and 29 negatively correlated. Mediation analysis highlighted the role of immune surveillance and metabolic dysregulation in tumor development, as evidenced by the association between the immune phenotype SSC-A on HLA DR+ NK cells and the metabolite 5-hydroxyhexanoate.The findings suggest significant causal relationships between immune phenotypes and malignant tumors of bone and articular cartilage, with metabolites potentially mediating these relationships. These insights lay the groundwork for further research and could contribute to the development of new biomarkers and treatment strategies.

    Keywords: Causal relationships, Immune Cell Features, Mendelian randomization, malignant tumors of bone and articular cartilage, Metabolites, Mediation analysis

    Received: 15 May 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Long, Gong, Zheng, Liu, Ying and Xiao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Tengfei Zheng, Shandong First Medical University, Tai'an, 271000, Shandong, China
    Zhendong Ying, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong Province, China
    Cong Xiao, Mianyang Third People's Hospital, Mianyang, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.