Research Paper Volume 15, Issue 15 pp 7565—7582
Unveiling the prognostic significance of SOX5 in esophageal squamous cell carcinoma: a comprehensive bioinformatic and experimental analysis
- 1 Department of Cardiothoracic Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
- 2 Department of Cardiothoracic Surgery, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian 223300, Jiangsu, China
- 3 Department of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian 223300, Jiangsu, China
Received: May 1, 2023 Accepted: July 10, 2023 Published: August 2, 2023
https://doi.org/10.18632/aging.204924How to Cite
Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: This study aimed to investigate the expression and prognostic significance of SOX5 in esophageal squamous cell carcinoma (ESCC).
Methods: Gene Expression Omnibus (GEO) data were analyzed to assess SOX5 expression in ESCC and normal tissues. Survival analysis was performed to evaluate its prognostic significance. Pathway enrichment analysis was conducted to identify pathways associated with low SOX5 expression. Methylation status of CpG sites in ESCC cases was examined, and SOX5 expression was evaluated. Differential expression and ChIP-seq data analyses were used to identify genes significantly correlated with SOX5 and to obtain target genes. A protein-protein interaction (PPI) network was constructed using hub genes, and their association with immune cell infiltration was determined. In vitro ESCC cell experiments validated the findings.
Results: SOX5 was significantly downregulated in ESCC samples compared to normal samples. Its downregulation was associated with shorter survival in ESCC patients. Pathway enrichment analysis revealed enrichment in regulated necrosis, NLRP3 inflammasome, formation of the cornified envelope, and PD-1 signaling. Methylation status of two CpG sites negatively correlated with SOX5 expression. Differential expression analysis identified 122 genes significantly correlated with SOX5, and 28 target genes were obtained from ChIP-seq analysis. Target genes were enriched in DNA replication, cell cycle, spindle, and ATPase activity. Five hub genes were identified, and the PPI network showed significant associations with immune cell infiltration. In vitro experiments confirmed SOX5 downregulation, upregulation of hub genes, and their functional effects on ESCC cell apoptosis and proliferation.
Conclusions: These findings enhance understanding of SOX5 in ESCC and potential therapeutic strategies.