Liu Xiaoyun, Yang Sen, Liu Liyun
Department of General Medical, The People's Hospital of Changzhi City, The Third Clinical Hospital of Changzhi Medical University, 502 Changxing Middle Road, Changzhi, Shanxi Province, 046000, China.
Department of Orthopedics, The People's Hospital of Changzhi City, The Third Clinical Hospital of Changzhi Medical University, 502 Changxing Middle Road, Changzhi, Shanxi Province, 046000, China.
BMC Cancer. 2025 May 9;25(1):852. doi: 10.1186/s12885-025-14281-y.
Changes in gut microbiota metabolism might play an important role in the development of some cancers. However, the causal relationships of gut microbiome-related metabolic pathways in chondrosarcomas and the specific pathways affected remain largely unknown.
We used two-sample bidirectional and multivariate Mendelian randomization (MR) to reveal a causal relationship between the gut microbiota metabolic pathway (GMMP) and chondrosarcoma associated gene 1(CSAG1) via the largest available genome-wide association study (GWAS).
Univariate MR analysis revealed that tetrapyrrole biosynthesis from glutamate, menaquinol 6 biosynthesis, glycogen degradation II, 8-amino-7-oxononanoate biosynthesis, taxadiene biosynthesis, glycolysis and tRNA charging had a significant causal relationship with CSAG1.Multivariate MR analysis suggested that tetrapyrrole biosynthesis, menaquinol 6 biosynthesis, glycogen degradation II, glycolysis and tRNA charging still had a significant causal effect on CSAG1. According to the results of reverse MR analysis, no significant causal effect of CSAG1 on the GMMP was found.
This study offers further insights into the gut microbiota-mediated mechanism of chondrosarcoma development.
肠道微生物群代谢的变化可能在某些癌症的发生发展中起重要作用。然而，在软骨肉瘤中肠道微生物群相关代谢途径的因果关系以及受影响的具体途径在很大程度上仍不清楚。
我们通过最大规模的全基因组关联研究（GWAS），采用两样本双向和多变量孟德尔随机化（MR）来揭示肠道微生物群代谢途径（GMMP）与软骨肉瘤相关基因1（CSAG1）之间的因果关系。
单变量MR分析显示，谷氨酸的四吡咯生物合成、甲基萘醌-6生物合成、糖原降解II、8-氨基-7-氧代壬酸生物合成、紫杉二烯生物合成、糖酵解和tRNA充电与CSAG1有显著的因果关系。多变量MR分析表明，四吡咯生物合成、甲基萘醌-6生物合成、糖原降解II、糖酵解和tRNA充电对CSAG1仍有显著的因果效应。根据反向MR分析结果，未发现CSAG1对GMMP有显著的因果效应。
本研究为软骨肉瘤发生发展的肠道微生物群介导机制提供了进一步的见解。
