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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Cancer Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1437197

Dissecting the importance and origin of circulating myokines in gastric cancer cachexia Running head: Myokines in gastric cancer cachexia

Provisionally accepted
Marek Sierzega Marek Sierzega 1*Anna Drabik Anna Drabik 2Marek Sanak Marek Sanak 1Robert Chrzan Robert Chrzan 1Piotr Richter Piotr Richter 1
  • 1 Jagiellonian University Medical College, Kraków, Poland
  • 2 Faculty of Materials Science and Ceramics, AGH University of Science and Technology, Krakow, Lesser Poland, Poland

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

    Some experimental data suggest that myokines may play an important role in developing cancer-associated cachexia (CAC), but their relevance in humans remains poorly explored. In our study, we tested the hypothesis that circulating myokines are associated with the pathogenesis of CAC in a model population of gastric cancer. A panel of 19 myokines was measured in portal and peripheral blood as well as tumour tissue and surrounding gastric mucosa. Moreover, a serum proteomic signature of cachexia was identified by a label-free quantitative proteomics with a nano LC-MS/MS system and stored in a ProteomeXchange database (PXD049334). The concentrations of fatty acid-binding protein 3 (FABP3), follistatin-like 1 protein (FSTL−1), interleukin 6 (IL 6), and interleukin 8 (IL 8) were significantly higher in the peripheral blood of cachectic subjects, while leptin levels were lower. Of all the evaluated myokines, tumour tissues showed higher expression levels only for IL-15 and myostatin. However, the analysis of paired samples failed to demonstrate a decreasing concentration gradient between the portal and peripheral blood for any of the myokines, evidencing against their release by the primary tumour. Proteomic analysis identified 28 proteins upregulated and 24 downregulated in the peripheral blood of patients with cachexia. Differentially expressed proteins and 5 myokines with increased serum levels generated a significant protein-protein interaction network. Taken together, our study provides clinical evidence that some myokines are involved in the pathogenesis of cachexia and are well integrated into the regulatory network of circulating blood proteins identified among cachectic patients with gastric cancer.

    Keywords: gastric cancer, Cachexia, Myokines, Interleukins, Fatty acid-binding protein 3, follistatin-like 1 protein

    Received: 23 May 2024; Accepted: 11 Sep 2024.

    Copyright: © 2024 Sierzega, Drabik, Sanak, Chrzan and Richter. 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: Marek Sierzega, Jagiellonian University Medical College, Kraków, Poland

    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.