Assessment of circulating proteins in thyroid cancer: Proteome-wide Mendelian randomization and colocalization analysis
Qinghua Fan,
Shifeng Wen,
Yi Zhang,
Xiuming Feng,
Wanting Zheng,
Xiaolin Liang,
Yutong Lin,
Shimei Zhao,
Kaisheng Xie,
Hancheng Jiang,
Haifeng Tang,
Xiangtai Zeng,
You Guo,
Fei Wang,
Xiaobo Yang
Affiliations
Qinghua Fan
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
Shifeng Wen
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
Yi Zhang
The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan, China
Xiuming Feng
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
Wanting Zheng
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
Xiaolin Liang
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
Yutong Lin
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
Shimei Zhao
The Second Affiliated Hospital of Guangxi University of Science and Technology, Liuzhou 545000, Guangxi, China
Kaisheng Xie
The Second Affiliated Hospital of Guangxi University of Science and Technology, Liuzhou 545000, Guangxi, China
Hancheng Jiang
Liuzhou Workers' Hospital, Liuzhou 545000, Guangxi, China
Haifeng Tang
The Second People’s Hospital of Yulin, Yulin 537000, Guangxi, China
Xiangtai Zeng
The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi, China
You Guo
The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi, China
Fei Wang
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; Corresponding author
Xiaobo Yang
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; Corresponding author
Summary: 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 (nCase = 3,418, nControl = 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 (PBH = 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.
