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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Cancer Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1446863
This article is part of the Research Topic Unraveling the Complex Interplay Between Aging, Immunity, Metabolites, and Metabolism in Endocrine-Related Cancers View all 7 articles

Inflammatory factors and risk of lung adenocarcinoma: a Mendelian randomization study mediated by blood metabolites

Provisionally accepted
Zheng Ding Zheng Ding Juan Chen Juan Chen Bohan Li Bohan Li *Xinyu Ji Xinyu Ji *
  • The First Affiliated Hospital of China Medical University, Shenyang, China

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

    Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer, and its pathogenesis remains not fully elucidated. Inflammation and metabolic dysregulation are considered to play crucial roles in LUAD development, but their causal relationships and specific mechanisms remain unclear.Methods: This study employed a two-sample Mendelian randomization (MR) approach to systematically evaluate the causal associations between 91 circulating inflammatory factors, 1,400 serum metabolites, and LUAD. We utilized LUAD genome-wide association studies (GWAS) data from the FinnGen biobank and GWAS data of metabolites and inflammatory factors from the GWAS catalog to conduct two-sample MR analyses. For the identified key metabolites, we further used mediator MR to investigate their mediating effects in the influence of IL-17A on LUAD and explored potential mechanisms through protein-protein interaction and functional enrichment analyses.Results: The MR analyses revealed that IL-17A (OR 0.78, 95%CI 0.62-0.99) was negatively associated with LUAD, while 71 metabolites were significantly associated with LUAD. Among them, ferulic acid 4-sulfate may play a crucial mediating role in the suppression of LUAD by IL-17A (OR 0.87, 95%CI 0.78-0.97). IL-17A may exert its anti-LUAD effects through extensive interactions with genes related to ferulic acid 4-sulfate metabolism (such as SULT1A1, CYP1A1, etc.), inhibiting oxidative stress and inflammatory responses, as well as downstream tumor-related pathways of ferulic acid 4-sulfate (such as MAPK, NF-κB, etc.).Conclusion: This study discovered causal associations between IL-17A, multiple serum metabolites, and LUAD occurrence, revealing the key role of inflammatory and metabolic dysregulation in LUAD pathogenesis. Our findings provide new evidencebased medical support for specific inflammatory factors and metabolites as early predictive and risk assessment biomarkers for LUAD, offering important clues for subsequent mechanistic studies and precision medicine applications.

    Keywords: Lung Adenocarcinoma, Inflammatory factors, Blood metabolites, causal inference, Mediation analysis, Mendelian randomization

    Received: 10 Jun 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Ding, Chen, Li and Ji. 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:
    Bohan Li, The First Affiliated Hospital of China Medical University, Shenyang, China
    Xinyu Ji, The First Affiliated Hospital of China Medical University, Shenyang, 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.