To investigate the expression and biological function of α-Galactosidase A (GLA) in esophageal squamous cell carcinoma (ESCC) and its role in chemotherapy resistance.
Approach:
Data Analysis: Utilized two independent ESCC datasets for gene screening, validated findings through single-cell RNA-seq, and assessed GLA expression via immunohistochemistry, qRT-PCR, and Western blot.
Functional Assays: Conducted siRNA-mediated knockdown of GLA and performed CCK-8, EdU, colony formation, Transwell, and wound healing assays to evaluate its biological function.
Enrichment Analyses: Performed KEGG, GO, and GSEA to explore underlying mechanisms and assessed the impact of GLA knockdown on chemosensitivity.
Combination Treatment Evaluation: Evaluated the effect of combining the GLA pharmacological chaperone Migalastat with gemcitabine or cisplatin on ESCC cell lines.
Key Findings:
GLA was significantly upregulated in ESCC and showed strong diagnostic performance across datasets.
GLA knockdown suppressed proliferation, colony formation, and migration of ESCC cells.
High GLA expression was associated with DNA damage repair and chemotherapy resistance-related genes.
GLA knockdown increased sensitivity of ESCC cells to gemcitabine and cisplatin.
Migalastat combined with chemotherapy enhanced cytotoxicity in ESCC cell lines.
Interpretation:
GLA is identified as an oncogenic factor in ESCC, linked to DNA damage repair mechanisms and chemotherapy response.
Limitations:
The study primarily relies on in vitro analyses, which may not fully replicate in vivo conditions.
Further mechanistic and in vivo investigations are needed to validate findings.
Conclusion:
GLA is a novel, upregulated gene in ESCC with diagnostic relevance and an oncogenic role.
