Abstract
Serum amyloid A-like 1 (SAAL1) was recently identified as a novel oncogene in hepatocellular carcinoma (HCC). To explore the potential role of SAAL1 in other cancers, we conducted a pan-cancer analysis of SAAL1 expression and its association with tumor microenvironment (TME) immunological profiles, sensitivity to chemotherapy agents, response to immunotherapy, and patient prognosis. SAAL1 was overexpressed in most malignant tumors in association with poor prognosis. Moreover, its expression was positively correlated with TME-relevant immune and mismatch signatures, immunostimulatory infiltrating cells (CD4+ memory T cells, activated NK cells, M1 macrophages, and cytotoxic CD8+ T cells), microsatellite instability (MSI), tumor mutational burden (TMB), neoantigen load, and immune checkpoint markers (PD-L1, LAG-3 and CTLA-4) in multiple cancers. SAAL1 overexpression was also associated with immunotherapy response and overall survival (OS) in bladder cancer (BLCA) patients who had received anti-PD-L1 treatment. Gene set enrichment analysis (GSEA) further showed significant enrichment of SAAL1 in immune cell signaling, cell cycle, and cell adhesion pathways. Moreover, we detected tumor-specific correlations between SAAL1 expression and either chemoresistance or sensitivity to common chemotherapeutics. Lastly, we showed that SAAL1 silencing suppresses both malignant phenotype and expression of PD-L1 in lung cancer A549 cells in vitro. These findings suggest that SAAL1 contributes to tumorigenesis and antitumor immunity mechanisms in different cancer types, and may thus serve as both a prognostic biomarker and potential target for cancer immunotherapy.