一些实验数据表明，肌因子可能在癌症相关恶病质 (CAC) 的发展中发挥重要作用，但其与人类的相关性仍未得到充分探索。在我们的研究中，我们在胃癌模型人群中测试了循环肌因子与 CAC 发病机制相关的假设。对 171 名未接受过治疗的胃腺癌患者进行了前瞻性检查。恶病质定义为体重减轻>5%或体重减轻>2%且BMI<20 kg/m2或肌肉减少症。在门静脉血和外周血以及肿瘤组织和周围胃粘膜中测量了一组 19 种肌因子。此外，使用纳米 LC-MS/MS 系统通过无标记定量蛋白质组学鉴定了恶病质的血清蛋白质组特征，并将其存储在 ProteomeXchange 数据库 (PXD049334) 中。一百名 (58%) 患者被诊断患有 CAC。恶病质受试者外周血中脂肪酸结合蛋白 3 (FABP3)、卵泡抑素样 1 蛋白 (FSTL-1)、白细胞介素 6 (IL 6) 和白细胞介素 8 (IL 8) 的浓度显着较高，而瘦素水平较低。在所有评估的肌因子中，肿瘤组织中仅 IL-15 和肌生长抑制素表现出较高的表达水平。然而，对配对样品的分析未能证明任何肌因子的门脉和外周血之间的浓度梯度降低，这证明了它们是由原发肿瘤释放的。蛋白质组学分析发现，恶病质患者的外周血中有 28 种蛋白质上调，24 种蛋白质下调。差异表达的蛋白质和血清水平升高的 5 种肌因子产生了显着的蛋白质-蛋白质相互作用网络。我们的研究提供了临床证据，表明一些肌因子参与恶病质的发病机制，并且很好地整合到恶病质患者中发现的循环血液蛋白的调节网络中患有胃癌。版权所有 © 2024 Sierzega、Drabik、Sanak、Chrzan 和 Richter。

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 group of 171 treatment naïve patients with adenocarcinoma of the stomach were prospectively examined. Cachexia was defined as weight loss >5% or weight loss >2% with either BMI <20 kg/m2 or sarcopenia. 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).One hundred (58%) patients were diagnosed with CAC. 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.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.Copyright © 2024 Sierzega, Drabik, Sanak, Chrzan and Richter.