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Background: Energy metabolism (EM) genes play crucial roles in tumor development and progression. While neuroblastoma (NBL) cells exhibit high proliferation rates requiring efficient energy metabolism, the underlying mechanisms remain incompletely understood.
Methods: Transcriptomic analysis of the TARGET-NBL dataset was performed to stratify samples based on EM-related gene expression. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were integrated to identify critical gene modules. Prognostic biomarkers were determined through univariate and multivariate Cox regression analyses. Functional enrichment analysis and drug prediction were conducted for the identified biomarkers. Expression levels of candidate genes (GRIA2, FBXO32, GNG12, and PHLDA2) were validated using qRT-PCR. The biological function of GNG12 was investigated through gain- and loss-of-function studies in neuroblastoma cell lines.
Results: The analysis identified 1,675 differentially expressed genes and two critical modules (MEblack and MEturquoise) through WGCNA. Four prognostic biomarkers (GRIA2, FBXO32, GNG12, and PHLDA2) were established and integrated into a nomogram with clinical parameters. Functional analysis revealed their involvement in extracellular matrix organization, DNA replication, and nucleocytoplasmic transport. Drug prediction identified potential therapeutic compounds targeting GRIA2 and FBXO32. Experimental validation demonstrated elevated expression of all four biomarkers in neuroblastoma cell lines compared to normal controls. Notably, GNG12 knockdown significantly suppressed while its overexpression enhanced proliferation and migration of SH-SY5Y cells.
Conclusions: This study identified and validated four EM-related prognostic biomarkers in neuroblastoma, with GNG12 functionally implicated in tumor cell proliferation and migration. These findings provide potential therapeutic targets and prognostic indicators for neuroblastoma management.
DOI: 10.7754/Clin.Lab.2025.250323
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