Expression of Signal Regulatory Protein Alpha in Tumor Cells is the Key Factor in Intrahepatic Cholangiocarcinoma.

Abstract

Signal-regulatory protein alpha (SIRPα) has recently garnered attention for its role in the immune system, commonly referred to as the "don't eat me" signal. However, the relationship between SIRPα expression in tumor cells and prognosis in patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC) has been scarcely reported. A total of 117 patients who underwent hepatectomy for ICC were enrolled in this study. Immunohistochemical staining was performed to evaluate SIRPα, programmed cell death-ligand 1 (PD-L1), and cluster of differentiation 8 (CD8). The relationships between SIRPα expression, clinicopathological characteristics, and patient outcomes were analyzed. The macrophage-SIRPα-positive group exhibited a higher rate of lymph node metastasis (p = 0.0013). The tumor-cell-SIRPα-positive group showed lower carcinoembryonic antigen levels (p = 0.0068) and fewer cases of the perihilar type (p = 0.0165). In multivariate analysis, SIRPα positivity in tumor cells was identified as an independent prognostic factor for both disease-free survival (p = 0.0198) and overall survival (p = 0.0089). Notably, SIRPα positivity in tumor cells showed no significant correlation with PD-L1 expression or CD8-positive tumor-infiltrating T cells in ICC. Our findings demonstrate that SIRPα expression in tumor cells is more critical than its expression in macrophages for predicting the prognosis of patients with ICC following hepatic resection.