Identifying Hub Genes Associated with Sex Disparities in Prolactinomas.

Area of Science:

• Endocrinology and Molecular Biology
• Genomics and Bioinformatics
• Immunology

Background:

• Male prolactinomas present greater invasiveness and resistance to dopamine agonists, complicating treatment.
• Understanding genetic factors contributing to sex disparities in prolactinomas is crucial for developing effective therapies.

Purpose of the Study:

• To identify sex-related hub genes in prolactinomas using bioinformatics approaches.
• To explore the regulatory networks, chromosomal localization, and immune function associations of these sex-specific genes.
• To validate findings in human prolactinoma samples and identify potential therapeutic biomarkers.

Main Methods:

• Weighted gene co-expression network analysis and differential gene expression analysis to identify sex-related hub genes.
• Bioinformatic analyses for gene localization, regulatory networks (transcription factors, microRNAs), and immune cell infiltration (CIBERSORT).
• Correlation analysis with immune checkpoint genes and validation using RT-qPCR on surgical prolactinoma samples.

Main Results:

• Identified 21 sex-related hub genes: nine Y chromosome and six autosomal genes in males, and six specific genes in females.
• Predicted involvement of transcription factors (REST, androgen receptor) and microRNAs (miR-27a-3p, miR-146a-5p) in regulating these genes.
• Observed significant infiltration of resting dendritic cells and naive CD4+ T cells in male prolactinomas, with distinct correlations between male hub genes and immune checkpoint molecules.

Conclusions:

• Distinct sets of male and female hub genes were identified in prolactinomas.
• Potential biomarkers for male prolactinomas include KDM5D, PDCD1, ELOA3BP, XRRA1, and SIGLEC12.
• Potential biomarkers for female prolactinomas include SOX3, DMGDH, and NPAS1, providing a basis for targeted therapeutic strategies.