A Pan-Cancer Analysis Reveals OAS2 as a Biomarker for Cancer Prognosis and Immunotherapy

Background: Although immunotherapy with immune checkpoint inhibitor has emerged as a remarkably effective treatment modality, it benefits only a small proportion of patients. Oligoadenylate Synthetase 2 (OAS2) has been implicated in various cancers, while the relationship between OAS2 expression, immune cell infiltration, and patient prognosis in pan-cancer remains unclear. Methods: : We conducted an analysis of OAS2 in pan-cancers using databases such as TCGA, GTEx, UALCAN, cBioPortal, TIMER2.0, TIDE, and GDSC2. Results: : OAS2 exhibited different expression patterns between cancer and adjacent normal tissues, with significant impacts on the prognosis of various cancers. High OAS2 expression correlated with poor overall survival (OS) and disease-specific survival (DSS) in low-grade glioma (LGG), pancreatic adenocarcinoma (PAAD), and testicular germ cell tumors (TGCT). Conversely, upregulated OAS2 expression was associated with favorable OS and disease-free survival (DFS) in ovarian cancer (OV) and skin cutaneous melanoma (SKCM). OAS2 expression was positively associated with B cell, CD4+ T cell, and CD8+ T cell infiltration in most cancers, except for LGG. Notably, in SKCM, OAS2 expression positively correlated with activated natural killer (NK) cell infiltration and inversely correlated with resting NK cell infiltration. Co-expression analyses indicated close associations between OAS2 and several common immune checkpoints. Higher OAS2 gene expression correlated with longer overall survival (OS) and progression-free survival (PFS) under immune checkpoint blockade (ICB) immunotherapy in two clinical cohorts. Conclusion: OAS2 is a promising biomarker for evaluating cancer prognosis, particularly in SKCM. Its association with immune factors and modulation of immune cell infiltration suggest its predictive potential for ICB immunotherapy.