Abstract

Craniopharyngiomas are rare epithelial tumors derived from pituitary gland embryonic tissue. This epithelial tumor can be categorized as an adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) subtype with histopathological and genetic differences. Genomic and transcriptomic profiles of craniopharyngiomas have been investigated; however, the proteomic profile has yet to be elucidated and added to these profiles. Recent improvements in high-throughput quantitative proteomic approaches have introduced new opportunities for a better understanding of these diseases and the efficient discovery of biomarkers. We aimed to confirm subtype-associated proteomic changes between ACP and PCP specimens. We performed a system-level proteomic study using an integrated approach that combines mass spectrometry-based quantitative proteomic, statistical, and bioinformatics analyses. The bioinformatics analysis showed that differentially expressed proteins between ACP and PCP were significantly involved in mitochondrial organization, fatty acid metabolic processes, exocytosis, the inflammatory response, the cell cycle, RNA splicing, cell migration, and neuron development. Furthermore, using network analysis, we identified hub proteins that were positively correlated with ACP and PCP phenotypes. Our findings improve our understanding of the pathogenesis of craniopharyngiomas and provide novel insights that may ultimately translate to the development of craniopharyngioma subtype-specific therapeutics.

Highlights

  • Craniopharyngiomas are rare epithelial tumors derived from pituitary gland embryonic tissue

  • The tumor volumes were larger in the subjects with adamantinomatous craniopharyngioma (ACP) than in those with papillary craniopharyngioma (PCP)

  • Considering t-test results for pairwise comparisons and employing a filtering strategy based on a permutation-based false discovery rate (FDR) < 0.1 and fold-change > 1.5, we identified 1164 proteins that showed significant differential expression, of which 431 were upregulated in the ACP samples and 733 were upregulated in the PCP samples (Fig, 2A,B, and Supplementary Table S3 online)

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Summary

Introduction

Craniopharyngiomas are rare epithelial tumors derived from pituitary gland embryonic tissue This epithelial tumor can be categorized as an adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) subtype with histopathological and genetic differences. A few genomics studies based on gene expression analysis have provided comprehensive insight into the molecular pathogenesis and distinguishing features of both CP ­subtypes[11,12]. A systems-wide understanding of the distinct molecular features of ACP and PCP using mass spectrometry (MS)-based proteomics is limited.

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