Programmed Cell Death 10 (PDCD10) Is a Candidate Tumor-associated Gene in Esophageal Squamous Cell Carcinoma.

Abstract

Background/aim: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with poor survival rates. Effective molecular-targeted therapies are urgently needed. This study aimed to identify novel candidate tumor-associated genes in ESCC by analyzing chromosomal amplification regions.

Materials and methods: DNA copy number variation (CNV) and mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE). Single-cell RNA sequencing data from Gene Expression Omnibus (GEO) were analyzed using Scanpy. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded (FFPE) ESCC tissues. PDCD10 was identified as a potential tumor-associated gene, and its association with clinicopathological factors and prognostic impact was evaluated using Kaplan-Meier survival and Cox regression analyses. Pathway analysis was performed to investigate the biological processes, and drug sensitivity profiling was conducted to identify compounds whose efficacy correlated with PDCD10 expression in ESCC cell lines.

Results: PDCD10, a signaling protein involved in cell proliferation and vascular development, showed significant amplification and over-expression in ESCC cases. High PDCD10 expression was associated with poor prognosis. Single-cell RNA sequencing confirmed its tumor-specific expression. GSEA revealed enrichment of mTORC1 signaling, E2F, and Myc target pathways in high PDCD10-expressing tumors. Drug sensitivity analysis identified Azelaic acid and Rebamipide as compounds whose efficacy correlated with PDCD10 expression in ESCC cell lines.

Conclusion: PDCD10 could be a novel tumor-associated gene associated with tumor progression and poor prognosis in ESCC. Azelaic acid and Rebamipide are candidate therapeutic agents targeting PDCD10.