发现催乳素瘤中与性别差异相关的中枢基因。

IF 1 4区 生物学 Q4 GENETICS & HEREDITY
Genetic testing and molecular biomarkers Pub Date : 2025-09-01 Epub Date: 2025-09-04 DOI:10.1177/19450265251375945
Yuan Zhang, Yuyang Peng, Chengcheng Wang, Hong Liang, Song Li, Hui Yang
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引用次数: 0

摘要

背景:男性催乳素瘤患者表现出更大的侵袭性,对多巴胺激动剂有耐药性,使治疗更具挑战性。本研究旨在探讨导致泌乳素瘤性别差异的潜在不同基因。材料与方法:采用加权基因共表达网络分析和差异表达基因分析鉴定与性别相关的枢纽基因。此外,通过生物信息学分析了解基因在染色体上的定位、基因调控网络、信号通路及其与免疫功能的关系,并在21例人类泌乳素瘤样本中得到验证。结果:共鉴定出21个与性别相关的枢纽基因。男性的枢纽基因包括9个Y染色体基因和6个常染色体基因,而女性有6个特定基因。使用NetworkAnalyst在线工具的进一步预测表明,转录因子(REST,雄激素受体)和microrna (miR-27a-3p, miR-146a-5p)可能参与调节上述与性别相关的中枢基因。CIBERSORT分析显示,男性泌乳素瘤中有明显的静息树突状细胞和初始CD4+ T细胞浸润。性相关枢纽基因与免疫检查点基因的相关性分析显示,男性枢纽基因与CD47、CEACAM1呈正相关,与CD28、TNFSF14、CD226呈强负相关。最后,我们的手术催乳素瘤样本中类似的基因表达变化被RT-qPCR证实。结论:在泌乳素瘤中,我们通过生物信息学分析确定了男性中心基因和女性中心基因。我们的研究结果提示,KDM5D、PDCD1、ELOA3BP、XRRA1、SIGLEC12可能是男性催乳素瘤的潜在生物标志物,而SOX3、DMGDH、NPAS1可能是女性催乳素瘤的潜在生物标志物,为靶向治疗提供了理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identifying Hub Genes Associated with Sex Disparities in Prolactinomas.

Background: Male patients with prolactinomas exhibit greater invasiveness, resistance to dopamine agonists, making treatment more challenging. This study aims to explore the potential different genes contributing to sex disparities in prolactinomas. Materials and Methods: Weighted gene co-expression network analysis and differential expressed genes analysis were performed to identify sex-related hub genes. In addition, bioinformatics analyses were conducted to understand gene localization on chromosomes, gene regulatory networks, signaling pathways, and their relationship with immune function, which was verified in 21 human prolactinoma samples. Results: A total of 21 sex-related hub genes were identified. The hub genes in males included nine Y chromosome genes and six autosomal genes, while females had six specific genes. Further predictions using the NetworkAnalyst online tool suggested that transcription factors (REST, androgen receptor) and microRNAs (miR-27a-3p, miR-146a-5p) may be involved in regulating the above sex-related hub genes. CIBERSORT analysis revealed that prolactinomas in males showed significant infiltration of resting dendritic cells and naive CD4+ T cells. Correlation analysis between sex-related hub genes and immune checkpoint genes indicated that male hub genes were positively correlated with CD47 and CEACAM1, while showing a strong negative correlation with CD28, TNFSF14, and CD226. Finally, similar changes of gene expression in our surgical prolactinoma samples were confirmed by RT-qPCR. Conclusions: In prolactinomas, the male hub genes and female hub genes are identified by our bioinformatics analysis. Our findings suggest that KDM5D, PDCD1, ELOA3BP, XRRA1, and SIGLEC12 serve as potential biomarkers for male prolactinomas, while SOX3, DMGDH, and NPAS1 may serve as potential biomarkers for female prolactinoma, providing a theoretical basis for targeted therapy.

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来源期刊
CiteScore
2.50
自引率
7.10%
发文量
63
审稿时长
1 months
期刊介绍: Genetic Testing and Molecular Biomarkers is the leading peer-reviewed journal covering all aspects of human genetic testing including molecular biomarkers. The Journal provides a forum for the development of new technology; the application of testing to decision making in an increasingly varied set of clinical situations; ethical, legal, social, and economic aspects of genetic testing; and issues concerning effective genetic counseling. This is the definitive resource for researchers, clinicians, and scientists who develop, perform, and interpret genetic tests and their results. Genetic Testing and Molecular Biomarkers coverage includes: -Diagnosis across the life span- Risk assessment- Carrier detection in individuals, couples, and populations- Novel methods and new instrumentation for genetic testing- Results of molecular, biochemical, and cytogenetic testing- Genetic counseling
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