Keywords
Expression
GAPDH
Biomarker
Submitted : 2024-09-15
Accepted : 2024-09-30
Published : 2024-10-15
Abstract
Background: The present study aimed to investigate the expression level of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and explore its prognostic value across 24 different human cancers. This investigation was conducted using comprehensive bioinformatics and in vitro approaches that involved multiple layers of analysis. Methods: GAPDH expression and methylation levels were assessed via bioinformatics tools and validated using cell lines through RNA sequencing and targeted bisulfite sequencing analyses. The potential prognostic significance of GAPDH was evaluated through the use of a Kaplan–Meier plotter. Additionally, cBioPortal was employed to investigate genetic alterations associated with this gene. Pathway analysis was conducted using DAVID. Furthermore, a correlation analysis between GAPDH expression and CD8+ T immune cells was performed using TIMER and CDT. Lastly, a gene-drug interaction network analysis was conducted using Cytoscape to examine the relationship between GAPDH and drugs. Results: The GAPDH was found commonly up-regulated in 24 types of human cancers and its up-regulation was significantly correlated with the poor relapse-free survival (RFS) and overall survival (OS) of BLCA, CESC, HNSC, KIRP, LIHC, and LUAD. This implies that GAPDH plays a significant role in the development of these cancers. The GAPDH up-regulation was also noticed to be associated with the different clinicopathological features of BLCA, CESC, HNSC, KIRP, LIHC, and LUAD patients. Pathway analysis has shown GAPDH involvement in different diverse pathways. Furthermore, notable correlations were observed between the expression of GAPDH and its promoter methylation level, genetic alterations, as well as the level of CD8+ T immune cells. Moreover, we identified significant regulatory drugs targeting GAPDH that have the potential to modulate its expression and potentially prevent conditions such as BLCA, CESC, HNSC, KIRP, LIHC, and LUAD. Conclusion: Based on our findings, GAPDH emerged as a promising diagnostic and prognostic biomarker for BLCA, CESC, HNSC, KIRP, LIHC, and LUAD.
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