Integrated bioinformatics analysis identifies neutrophils and villous cytotrophoblasts infiltration characterized by BLC6 upregulation as associated with the co-occurrence of gestational diabetes mellitus and pre-eclampsia.

Background: Gestational diabetes mellitus (GDM) patients are one of the important high-risk groups for the development of pre-eclampsia (PE). The pathogenesis of PE in GDM patients is not fully understood. This study aims to identify hub genes and pathways associated with the co-occurrence of GDM and PE.

Methods: The matrix files of GDM and PE datasets were downloaded from GEO to identify differentially expressed genes (DEGs). The common DEGs were predicted for functional analysis through GO and KEGG analysis. A protein-protein interaction (PPI) network was constructed to determine the common hub genes for GDM and PE. Diagnostic hub genes were obtained through regression modeling and ROC analysis, and validated in publicly available datasets. The differences in immune infiltration between GDM and PE were analyzed. The expression and role of common hub genes in the co-occurrence of GDM and PE were explored through analysis of single-cell sequencing data.

Results: A total of 104 DEGs were identified between GDM and PE. These common DEGs were found to be involved in mucosal immune response and the JAK-STAT signaling pathway. A total of 27 common hub genes were identified for both GDM and PE. BCL6, DNAH9, and SCG2 were identified as potential diagnostic biomarkers for PE. BCL6 showed high expression in neutrophils and villous cytotrophoblasts (VCTs) in both PE and GDM.

Conclusion: This study identified BCL6, DNAH9, and SCG2 as common hub genes in GDM and PE. BCL6 is expected to be a new target for the diagnosis and treatment of GDM concurrent with PE.