发现男性特有的生物标志物，并揭示中枢性性早熟中与性别相关的代谢差异。
Discover boy specific-biomarkers and reveal gender-related metabolic differences in central precocious puberty.
机构信息
Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian 361005, China.
Department of Child Health, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian 361003, China.
出版信息
J Steroid Biochem Mol Biol. 2023 Jul;231:106305. doi: 10.1016/j.jsbmb.2023.106305. Epub 2023 Mar 28.
The incidence of central precocious puberty (CPP) in boys is rising, but lack of effective molecular biomarkers often leads to delayed treatment and thus the terrible clinical complications in adulthood. This study aims to identify the specific-biomarkers of CPP boys and understand the gender-related differences in metabolic characteristics of CPP. The specific-biomarkers of CPP boys were identified from serum by cross-metabolomics combined with linear discriminant analysis effect size analysis after age correction, and union receiver operating characteristic curve analyses were perform to optimize the combination of specific-biomarkers. The differences in metabolic characteristics between boys and girls with CPP were explored by cross-metabolomics and weighted gene co-expression network analysis. Results show that CPP activated in advance the HPG axis and induced gender-related clinical phenotypes. Seven serum metabolites were identified as specific-biomarkers of CPP boys, including acetoacetate, aspartate, choline, creatinine, myo-inositol, N,N-dimethylglycine and N-Acetyl-glycoprotein. The combination of aspartate, choline, myo-inositol and creatinine achieved an optimized diagnosis, where AUC is 0.949, prediction accuracy for CPP boys is 91.1%, and the average accuracy is 0.865. The metabolic disorders of CPP boys mainly involve in glycerophospholipid metabolism, and synthesis and degradation of ketone bodies. Betaine, glutamine, isoleucine, lactate, leucine, lysine, pyruvate, α-&β-glucose were identified as gender-related biomarkers for CPP, and they are mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, and alanine, aspartate and glutamate metabolism. Biomarkers combination provides a promising diagnostic potential for CPP boy with a favorite sensitivity and specificity. In addition, the differences of metabolic characteristics between boys and girls with CPP will contribute to the development of individualized clinical treatments in CPP.
中枢性性早熟（CPP）男孩的发病率正在上升，但缺乏有效的分子生物标志物往往导致治疗延迟，从而在成年期出现可怕的临床并发症。本研究旨在确定 CPP 男孩的特定生物标志物，并了解 CPP 代谢特征的性别差异。通过交叉代谢组学结合线性判别分析效应大小分析，在年龄校正后从血清中鉴定 CPP 男孩的特定生物标志物，并进行联合接收者操作特征曲线分析以优化特定生物标志物的组合。通过交叉代谢组学和加权基因共表达网络分析探索 CPP 男孩和女孩之间的代谢特征差异。结果表明，CPP 提前激活 HPG 轴并诱导性别相关的临床表型。鉴定出 7 种血清代谢物作为 CPP 男孩的特定生物标志物，包括乙酰乙酸、天冬氨酸、胆碱、肌酐、肌醇、N,N-二甲基甘氨酸和 N-乙酰糖蛋白。天冬氨酸、胆碱、肌醇和肌酐的组合达到了优化诊断，AUC 为 0.949，CPP 男孩的预测准确率为 91.1%，平均准确率为 0.865。CPP 男孩的代谢紊乱主要涉及甘油磷脂代谢和酮体的合成和降解。甜菜碱、谷氨酰胺、异亮氨酸、乳酸、亮氨酸、赖氨酸、丙酮酸、α-和β-葡萄糖被确定为 CPP 的性别相关生物标志物，它们主要参与糖酵解/糖异生、丙酮酸代谢以及丙氨酸、天冬氨酸和谷氨酸代谢。生物标志物组合为 CPP 男孩提供了有前途的诊断潜力，具有较高的敏感性和特异性。此外，CPP 男孩和女孩之间代谢特征的差异将有助于 CPP 个体化临床治疗的发展。
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