Department of Urology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Rhinology, FirstAffiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Immunol. 2024 Aug 29;15:1459967. doi: 10.3389/fimmu.2024.1459967. eCollection 2024.
Kidney cancer (KC) is a significant health burden globally, with over 400,000 new cases estimated in 2020. The prognosis of KC is influenced by various factors, including tumor spread, pathological characteristics, and molecular genetic changes. Recent studies have emphasized the involvement of gut microbiota and the immune system's contribution in the onset of KC. This extensive research endeavor sought to investigate the potential associations between diverse immune cell phenotypes, specific gut microbiota species, and their impact on the risk of developing KC, alongside the examination of circulating inflammatory proteins.
Adhering to the STROBE-MR guidelines, our investigation involved a two-stage Mendelian randomization (2SMR) analysis grounded on three fundamental assumptions: relevance, independence, and exclusion restriction. The exposure data utilized in this study originated from genome-wide association studies (GWAS) specifically designed to explore immune traits, inflammatory proteins, and gut microbiota compositions.
Our analysis identified 25 immune phenotypes, 4 circulating inflammatory proteins, and 12 gut microbiota features that exhibited significant causal associations with KC (P < 0.05). 10 immune phenotypes were protective against KC, while 15 were risk factors. Among the inflammatory proteins, CCL28 and IL-2 were protective, whereas FGF-23 and β-NGF were risk factors. Gut microbiota features associated with reduced KC risk included biosynthetic pathways involving amino acids and specific bacterial genera, whereas others, like Butyrivibrio crossotus and Odoribacter splanchnicus, were risk factors.
Immune, inflammatory, and gut microbiota factors impact KC development. Identified factors hint at biomarkers and therapeutic targets. It is very important to understand the relationship between these factors and KC.
全球范围内，肾癌（KC）是一个重大的健康负担，据估计，2020 年新发病例超过 40 万。KC 的预后受多种因素影响，包括肿瘤扩散、病理特征和分子遗传变化。最近的研究强调了肠道微生物群和免疫系统在 KC 发病中的作用。这项广泛的研究旨在探讨不同免疫细胞表型、特定肠道微生物物种与 KC 发病风险之间的潜在关联，以及循环炎症蛋白的作用。
本研究遵循 STROBE-MR 指南，采用两阶段孟德尔随机化（2SMR）分析，基于三个基本假设：相关性、独立性和排除限制。本研究使用的暴露数据来自专门用于探索免疫特征、炎症蛋白和肠道微生物群组成的全基因组关联研究（GWAS）。
我们的分析确定了 25 种免疫表型、4 种循环炎症蛋白和 12 种肠道微生物特征与 KC 有显著的因果关联（P<0.05）。其中 10 种免疫表型对 KC 具有保护作用，15 种为危险因素。在炎症蛋白中，CCL28 和 IL-2 具有保护作用，而 FGF-23 和 β-NGF 则为危险因素。与降低 KC 风险相关的肠道微生物特征包括涉及氨基酸的生物合成途径和特定细菌属，而其他如 Butyrivibrio crossotus 和 Odoribacter splanchnicus 则为危险因素。
免疫、炎症和肠道微生物群因素影响 KC 的发生。确定的因素提示了生物标志物和治疗靶点。了解这些因素与 KC 之间的关系非常重要。
