Bioinformatic Analysis of Gene Expression Related to Sialic Acid Biosynthesis in Patients With Medulloblastoma

Cureus. 2024 May 9;16(5):e59997. doi: 10.7759/cureus.59997. eCollection 2024 May.

Abstract

Background Sialic acid, a critical component for cell membrane integrity, undergoes complex biosynthesis involving enzymes like sialyltransferases (STs), impacting cancer progression. Aberrant sialylation by STs is implicated in cancer growth, invasion, and therapy resistance. Medulloblastoma (MB), a pediatric brain tumor with distinct subgroups and variable genetic alterations, poses uncertainty regarding the implications of sialylation. Methodology This study employs bioinformatic analyses on bulk and single-cell RNA-sequenced samples to explore atypical gene expressions linked to sialic acid metabolism in MB. A list of sialic biosynthesis-related genes was compiled using the STRING database. Data of MB samples from bulk and single-cell RNA sequencing were obtained from open-source repositories and were differentially analyzed, focusing on molecular subgroups (WNT, SHH, Group 3, and Group 4). The study employed survival analyses, specifically Cox regression, to analyze the overall survival (OS) data obtained through bulk RNA sequencing. Results Thirty-eight genes/proteins related to sialic acid metabolism were identified. Differential expression analysis between WNT and Group 3 and WNT and Group 4 revealed significant differences in seven and eleven genes, respectively, with consistent ST6GAL2 expression disparities (false discovery rate [FDR] P-value < 0.01, log2FC > 0.58). Elevated ST6GAL2 expression correlated with improved OS, with mortality risk reductions ranging from 26% to 48% (P-value < 0.006, Bonferroni-corrected threshold). Conclusions Elevated ST6GAL2 expression correlated with improved OS in diverse MB sample subsets, suggesting potential mechanisms in inhibiting tumor progression and enhancing immune response, requiring experimental validation.

Keywords: bioinformatic analysis; gene expression; medulloblastoma; rna sequence; sialic acid.

Grants and funding

The editing and publication services were supported by Grant-in-Aid for Early-Career Scientists Number 24K19553, awarded to Dr. Mudathir Bakhit by the Japanese Ministry of Education, Culture, Sports, Science, and Technology.