Proteomic Analyses Reveal Functional Pathways and Potential Targets in Pediatric Hydrocephalus

Abstract

Introduction: Hydrocephalus is a common pediatric disorder of cerebral spinal fluid physiology resulting in abnormal expansion of the cerebral ventricles. However, the underlying molecular mechanisms remain unknown.

Methods: We performed proteomic analyses of cerebrospinal fluid (CSF) from 7 congenital hydrocephalus and 5 arachnoid cyst patients who underwent surgical treatment. Differentially expressed proteins (DEPs) were identified by label-free Mass Spectrometry followed by differential expression analysis. The GO and GSEA enrichment analysis was performed to explore the cancer hallmark pathways and immune-related pathways affected by DEPs. Then, network analysis was applied to reveal the location of DEPs in the human protein-protein interactions (PPIs) network. Potential drugs for hydrocephalus were identified based on drug-target interaction.

Results: We identified 148 up-regulated proteins and 82 down-regulated proteins, which are potential biomarkers for clinical diagnosis of hydrocephalus and arachnoid cyst. Functional enrichment analysis revealed that the DEPs were significantly enriched in the cancer hallmark pathways and immunerelated pathways. In addition, network analysis uncovered that DEPs were more likely to be located in the central regions of the human PPIs network, suggesting DEPs may be proteins that play important roles in human PPIs. Finally, we calculated the overlap of drug targets and the DEPs based on drugtarget interaction to identify the potential therapeutic drugs of hydrocephalus.

Conclusion: The comprehensive proteomic analyses provided valuable resources for investigating the molecular pathways in hydrocephalus, and uncovered potential biomarkers for clinical diagnosis and therapy.

Keywords: DEPs; Proteomic; drugs; molecular pathways; pediatric hydrocephalus; proteins.