Fan Qinghua, Wen Shifeng, Zhang Yi, Feng Xiuming, Zheng Wanting, Liang Xiaolin, Lin Yutong, Zhao Shimei, Xie Kaisheng, Jiang Hancheng, Tang Haifeng, Zeng Xiangtai, Guo You, Wang Fei, Yang Xiaobo
The School of Public Health, Guangxi Medical University, Nanning 530000, Guangxi, China.
Guangxi Key Laboratory on Precise Prevention and Treatment for Thyroid Tumor, The Second Affiliated Hospital, Guangxi University of Science and Technology, Liuzhou 545000, Guangxi, China.
iScience. 2024 May 20;27(6):109961. doi: 10.1016/j.isci.2024.109961. eCollection 2024 Jun 21.
The causality between circulating proteins and thyroid cancer (TC) remains unclear. We employed five large-scale circulating proteomic genome-wide association studies (GWASs) with up to 100,000 participants and a TC meta-GWAS (n = 3,418, n = 292,703) to conduct proteome-wide Mendelian randomization (MR) and Bayesian colocalization analysis. Protein and gene expressions were validated in thyroid tissue. Through MR analysis, we identified 26 circulating proteins with a putative causal relationship with TCs, among which NANS protein passed multiple corrections ( = 3.28e-5, 0.05/1,525). These proteins were involved in amino acids and organic acid synthesis pathways. Colocalization analysis further identified six proteins associated with TCs (VCAM1, LGMN, NPTX1, PLEKHA7, TNFAIP3, and BMP1). Tissue validation confirmed BMP1, LGMN, and PLEKHA7's differential expression between normal and TC tissues. We found limited evidence for linking circulating proteins and the risk of TCs. Our study highlighted the contribution of proteins, particularly those involved in amino acid metabolism, to TCs.
循环蛋白与甲状腺癌（TC）之间的因果关系仍不明确。我们采用了五项大规模循环蛋白质组全基因组关联研究（GWAS），参与者多达100,000名，并进行了一项甲状腺癌元GWAS（n = 3,418，n = 292,703），以进行蛋白质组范围的孟德尔随机化（MR）和贝叶斯共定位分析。在甲状腺组织中验证了蛋白质和基因表达。通过MR分析，我们鉴定出26种与甲状腺癌存在假定因果关系的循环蛋白，其中NANS蛋白通过了多次校正（P = 3.28e-5，0.05/1,525）。这些蛋白质参与氨基酸和有机酸合成途径。共定位分析进一步鉴定出六种与甲状腺癌相关的蛋白质（VCAM1、LGMN、NPTX1、PLEKHA7、TNFAIP3和BMP1）。组织验证证实了BMP1、LGMN和PLEKHA7在正常组织和甲状腺癌组织之间的差异表达。我们发现循环蛋白与甲状腺癌风险之间的关联证据有限。我们的研究强调了蛋白质，特别是那些参与氨基酸代谢的蛋白质对甲状腺癌的作用。
