Xia Haodong, Li Yaohan, Liu Shengzhi, Han Haote, Zhou Chaoting, Wang Luyang, Jing Qiangan, Tian Jingkui, Tong Xiangmin, Wang Ying, Zhu Wei
The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 310002 Hangzhou, Zhejiang, China.
College of Biomedical Engineering and Instrument Science, Zhejiang University, 310027 Hangzhou, Zhejiang, China.
Front Biosci (Landmark Ed). 2022 Mar 8;27(3):90. doi: 10.31083/j.fbl2703090.
Thyroid dysfunction, including hypothyroidism (THO) and hyperthyroidism (THE), commonly arise from pathological processes in the thyroid gland. The current diagnosis of thyroid dysfunction varies because of the age and sex of the patients. The aim of this study was to explore novel candidate biomarker panels for hypothyroidism and hyperthyroidism screening with mass spectrometry and bioinformatics.
Plasma samples were collected from 15 THE patients, 9 THO patients, and 15 healthy controls. Data Independent Acquisition(DIA)-based proteomic and untargeted metabolomic analyses were performed to identify novel biomarker panels for THO and THE patients. Finally, three candidate biomarkers were verified by ELISA in 34 samples.
A total of 2738 proteins and 6103 metabolites were identified, and 173 proteins and 2487 metabolites were found to be differentially expressed among the THE, THO and control groups. The results of the ensemble feature selection, K-means clustering and least absolute shrinkage and selection operator (LASSO) regression model showed that two proteins (C4-A and C3/C5 convertase) combined with two metabolites (L-arginine and L-proline), and proteins (APOL1 and ITIH4) combined with metabolites (cortisol, and cortisone) identified by plasma proteomics and metabolomics could help distinguish THO and THE patients from healthy controls, respectively.
This study identified and verified two pairs of biomarker panels that can be used to distinguish THE and THO patients regardless of age and sex. Consequently, our findings represent a comprehensive analysis of thyroid dysfunction plasma, which is significant for clinical diagnosis.
甲状腺功能障碍，包括甲状腺功能减退（THO）和甲状腺功能亢进（THE），通常源于甲状腺的病理过程。由于患者的年龄和性别，目前甲状腺功能障碍的诊断存在差异。本研究的目的是通过质谱和生物信息学探索用于甲状腺功能减退和甲状腺功能亢进筛查的新型候选生物标志物组。
收集了15例THE患者、9例THO患者和15名健康对照者的血浆样本。进行基于数据独立采集（DIA）的蛋白质组学和非靶向代谢组学分析，以鉴定THO和THE患者的新型生物标志物组。最后，通过酶联免疫吸附测定（ELISA）在34个样本中验证了三种候选生物标志物。
共鉴定出2738种蛋白质和6103种代谢物，发现173种蛋白质和2487种代谢物在THE、THO和对照组之间存在差异表达。整体特征选择、K均值聚类和最小绝对收缩和选择算子（LASSO）回归模型的结果表明，两种蛋白质（C4 - A和C3/C5转化酶）与两种代谢物（L - 精氨酸和L - 脯氨酸），以及血浆蛋白质组学和代谢组学鉴定出的蛋白质（载脂蛋白L1和富含亮氨酸的α-2糖蛋白4）与代谢物（皮质醇和可的松）可分别帮助将THO和THE患者与健康对照区分开来。
本研究鉴定并验证了两对可用于区分THE和THO患者的生物标志物组，而不受年龄年龄年龄和性别的影响。因此，我们的研究结果代表了对甲状腺功能障碍血浆的综合分析，对临床诊断具有重要意义。
