Development of Serum Cell-Free miRNA Panel for Identification of Central Precocious Puberty and Premature Thelarche in Girls

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Yifen Shen¹, Yanping Hu², Tao Yang³, Hao Shen^4,a*, Genhai Shen^5,b*, Yuriy L. Orlov^6,7,c*, Shasha Zhou^8,d*, Yihang Shen^1,e*

¹Central laboratory, Suzhou Bay Clinical College, Xuzhou Medical University, Suzhou Ninth People’s Hospital, Suzhou, Jiangsu, 215200, China

²Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450008, China

³Department of Medical Cosmetology, Suzhou Ninth People’s Hospital, Suzhou, Jiangsu, 215200, China

⁴Clinical Laboratory, Suzhou Ninth People’s Hospital, Suzhou, Jiangsu, 215200, China

⁵Department of General Surgery, Suzhou Ninth People’s Hospital, Suzhou, Jiangsu, 215200, China

⁶Digital Health Center, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), 119991 Moscow, Russia

⁷Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

⁸Department of Endocrinology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, 200040, China

^* To whom correspondence should be addressed.

Received: July 23, 2024; Revised: September 11, 2024; Accepted: September 15, 2024

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Precocious puberty of children, especially girls, has attracted more and more public attention in recent years. In clinic practice, there is a lack of both convenient and effective way to identify central precocious puberty (CPP) and premature thelarche (PT). In this study, we enrolled total 88 girls [28 cases of CPP, 37 cases of PT, as well as 23 cases of normal control (NC)] as a training cohort, and another 270 subjects (92 cases of CPP, 122 cases of PT and 56 cases of NC) as a validation cohort. Expression of serum cell-free miRNA in the training cohort was analyzed using five different methods to identify specific miRNA feature subsets, and verified by qPCR in the validation cohort. Here, we determined that the combination of miRNAs (miR-584-5p, miR-625-3p, miRNA-652-3p, miR-22-3p) provided the possibility to distinguish CPP and PT. The miRNA panel (miR-625-3p, let-7b-5p, miR-140-5p, miR-7-5p) had the best performance in distinguishing between CPP and NC. The miRNA panel (miR-140-5p, miR-205-5p, let-7b-5p, miR-629-5p, miR-9-3p) performed well in identifying PT and NC. Based on the absolute quantification of miRNA by qPCR, we also presented three regression equations to evaluate CPP, PT, and NC, respectively, for possible use in clinical practice. The presented study had identified several sets of miRNA panels as biomarkers to assist in identifying CPP and PT. Our invention could provide better diagnostic tool for pediatric precocious puberty diseases in both clinical and public health fields.

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KEY WORDS: central precocious puberty, premature thelarche, serum cell-free miRNA

DOI: 10.1134/S0006297924100134

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