Tang Hong, Tang Na, Liao Yueling, Tan Tao, Xie Hui, Wang Jiong, Hui Xie
Department of Spine surgery, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, P. R. China.
Department of Cardiovascular medicine, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, P. R. China.
Discov Oncol. 2025 Jul 31;16(1):1448. doi: 10.1007/s12672-025-03283-8.
To investigate the causal relationship between 91 circulating inflammatory proteins and osteosarcoma using the two-sample Mendelian randomization method.
Corresponding exposure and outcome data were extracted from genome-wide association study (GWAS) databases. A two-sample Mendelian randomization analysis was conducted on the data, with the inverse-variance weighted (IVW) method serving as the primary analytical approach. This was complemented by MR-Egger, weighted median, simple mode, and weighted mode methods to validate the results. Sensitivity analyses were also performed to verify the reliability of the data.
The IVW analysis revealed a positive causal relationship between GCST90274776 (OR = 3.02, 95% CI: 0.033-0.117, P = 0.028), GCST90274822 (OR = 1.603, 95% CI: 1.014-2.535, P = 0.043), and GCST90274847 (OR = 2.580, 95% CI: 1.155-5.762, P = 0.021) and osteosarcoma. In contrast, GCST90274844 (OR = 0.313, 95% CI: 0.155-0.634, P = 0.001) showed a negative causal relationship with osteosarcoma. The supplementary analysis methods (MR-Egger, weighted median, simple mode, and weighted mode) consistently validated the direction and magnitude of these findings. The sensitivity analysis indicated that the data were reliable and free from bias.
Using the Mendelian randomization approach, this study suggest that GCST90274776, GCST90274822, and GCST90274847 may be risk factors for osteosarcoma, whereas GCST90274844 appears to exhibit a protective effect against the disease.
采用两样本孟德尔随机化方法研究91种循环炎症蛋白与骨肉瘤之间的因果关系。
从全基因组关联研究（GWAS）数据库中提取相应的暴露和结局数据。对数据进行两样本孟德尔随机化分析，以逆方差加权（IVW）方法作为主要分析方法。并用MR-Egger、加权中位数、简单模式和加权模式方法对结果进行验证。还进行了敏感性分析以验证数据的可靠性。
IVW分析显示，GCST90274776（OR = 3.02，95%CI：0.033 - 0.117，P = 0.028）、GCST90274822（OR = 1.603，95%CI：1.014 - 2.535，P = 0.043）和GCST90274847（OR = 2.580，95%CI：1.155 - 5.762，P = 0.021）与骨肉瘤之间存在正因果关系。相反，GCST90274844（OR = 0.313，95%CI：0.155 - 0.634，P = 0.001）与骨肉瘤呈负因果关系。补充分析方法（MR-Egger、加权中位数、简单模式和加权模式）一致验证了这些发现的方向和程度。敏感性分析表明数据可靠且无偏差。
本研究采用孟德尔随机化方法表明，GCST90274776、GCST90274822和GCST90274847可能是骨肉瘤的危险因素，而GCST90274844似乎对该病具有保护作用。
