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Expression of ATG5 and PDIA3 in cervical cancer tissues and their clinical significance
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Abstract:
Objective：To investigate the expression of immunogenic cell death-related genes, autophagy associated gene 5 (ATG5) and protein disulfide isomerase A3 (PDIA3), in cervical cancer tissues, and to explore their correlation with clinicopathological features and prognosis of cervical cancer patients, as well as the related signaling pathways and drug sensitivity. Methods: A total of 60 cervical cancer tissue specimens from the patients treated at Affiliated Hospital of Qingdao University during January 2016 and December 2023 were collected as the experimental group. Additionally, 26 normal cervical specimens collected from patients with hysteromyoma and adenomyosis served as the control group. The data of two groups of patients were also collected. The differential protein expression of ATG5 and PDIA3 in cervical cancer tissues and normal cervical tissues was detected by immunohistochemistry, and their relationship with patients' clinicopathological parameters was also analyzed. The influence of ATG5 and PDIA3 expression in cervical cancer tissues on patient prognosis was analyzed using interactive analysis platform (GEPIA). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were utilized to explore their functional roles and signaling pathways associated with ATG5 and PDIA3 genes. The sensitivity of cervical cancer patients to chemotherapeutic drugs was analyzed using the pRRophetic package based on the high and low expression of ATG5 and PDIA3 in cancer tissues. Results: The positive expression rates of ATG5 and PDIA3 in cervical cancer tissues were significantly higher than those in normal cervical tissues (83.3% vs 11.5%, χ 2 = 39.538, P = 0.001; 75.0% vs 46.2%, χ 2 = 6.753, P = 0.009). The expression levels of ATG5 differed notably across patients with different tumor diameter, FIGO stage and lymph node metastasis (all P < 0.01), while the expression levels of PDIA3 differed greatly across patients with different tumor diameter, differentiation degree, FIGO stage and lymph node metastasis (P < 0.05 or P < 0.01). The expression levels of ATG5 and PDIA3 were positively correlated (r = 0.679, P < 0.001). Prognostic analysis via GEPIA showed that high ATG5 and PDIA3 expression correlated with poor prognosis in cervical cancer patients (all P < 0.05). Key enriched functions and signaling pathways for ATG5 and PDIA3 included cell proliferation and differentiation, antigen processing and presentation, P53 binding, Wnt signaling pathway, MAPK signaling pathway and mTOR signal pathway. Conclusion: ATG5 and PDIA3 are highly expressed in cervical cancer tissues, with their elevated expression is associated with poor prognosis. Both ATG5 and PDIA3 are involved in cell proliferation and differentiation, antigen processing and presentation, and various signaling pathways, making them potential targets for cervical cancer treatment.
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