Expression of cluster of differentiation 47 (CD47) and signal regulatory protein alpha (SIRPα) as prognostic biomarkers and potentially therapeutic targets in esophageal squamous cell carcinoma.

Background: The cluster of differentiation 47 (CD47)-signal regulatory protein alpha (SIRPα) axis is a key regulator of innate immune surveillance, facilitating the neoplastic evasion of macrophage-mediated phagocytosis. Although this pathway has been implicated in tumor immune escape in multiple malignancies, its clinical and prognostic significance in esophageal squamous cell carcinoma (ESCC) remain to be fully elucidated.

Methods: We retrospectively analyzed 100 patients who underwent esophagectomy for resectable ESCC. Immunohistochemical testing determined SIRPα expression in peritumoral immune infiltrates and CD47 expression in tumor and immune cells, while tumor proportion score (TPS) and combined positive score (CPS) were used to evaluate CD47 staining. Survival outcomes and correlations with clinicopathological factors were also analyzed.

Results: Increased expression of SIRPα, CD47 CPS, and CD47 TPS was detected in 47, 50, and 47% of patients, respectively. Elevated SIRPα expression was significantly associated with decreased overall survival. Also increased CD47 CPS and TPS was significantly associated with decreased overall survival and relapse-free survival. CD47 CPS was identified as an independent prognostic indicator for overall survival in multivariate Cox regression analysis (hazard ratio [HR] = 3.89; 95% confidence interval [CI] = 1.57-9.61; P = 0.003). Patients with concurrent high expression of both SIRPα and CD47 CPS demonstrated the poorest survival outcomes.

Conclusion: Overexpression of SIRPα and CD47, especially in tandem, is associated with poor clinical outcomes in ESCC, suggesting that the CD47-SIRPα axis may serve as a useful prognostic biomarker and a potential therapeutic target for newly immune checkpoint blockade in ESCC.