High expression of caspase-8 as a predictive factor of poor prognosis in patients with esophageal cancer

Background: Esophageal carcinoma (ESCA) is considered to be one of the most common gastrointestinal cancers. Caspase-8 (CASP8) is a key protein of cross-talk signaling in a variety of cancers. However, the role of CASP8 expression in the prognosis of patients with ESCA has remained unexplored. Hence, it is needed to explore the clinical significance of CASP8 expression in ESCA.

Methods: The expression and prognosis of CASP8 were investigated in ESCA using the UALCAN, GEDS, TIMER, and OncoLnc databases. The CASP8 genetic variations in ESCA were assessed using the cBioPortal database. The correlation between CASP8 expression and tumor immune invasion and immune cell surface indicators was examined using the TIMER and TISIDTISIDB datasets. Meanwhile, the abundance of the immunological cells in the tumor and healthy tissues was assessed by the CIBERSORT method. Next, information on the co-expressed genes of the differentially expressed genes (DEGs) in ESCA-tumor and ESCA-healthy tissues was obtained using the cBioPortal, UALCAN, and Coexpedia databases. Subsequently, the PPI network was constructed and the GO and KEGG pathways were analyzed using the SIRING database. Finally, CASP8 mRNA and protein expression in the ESCA tissues and matched adjacent healthy tissues were analyzed using qRT-PCR, immune-blotting, and immunohistochemistry. Additionally, the relationship between clinicopathological features and CASP8 expression was assessed.

Results: ESCA tissues had higher levels of CASP8 mRNA and protein expression compared to healthy tissues. patients with an elevated level of CASP8 expression had poor overall survival (OS). CASP8 expression was significantly correlated with the degree of differentiation (P = 0.004) and lymph node metastasis (P = 0.044). There were diverse patterns of association between immunological cell surface biomarkers and CASP8 expression.

Conclusion: ESCA showed significant levels of CASP8 expression which may serve as a prognostic biomarker correlated to immune infiltrates in ESCA.