Predicting ovarian cancer prognosis and immunotherapy response through siglec15 and PD-L1 expression analysis.

BACKGROUND: Ovarian cancer (OC) is a highly aggressive malignancy often diagnosed in advanced stages. This study investigates the expression patterns and prognostic significance of Siglec15 and PD-L1 in OC, with the aim of developing a novel prognostic tool and exploring potential targets for treatment. METHODS: Patients with OC were categorized into subgroups for analysis of tumor microenvironment and immune cell infiltration using the ESTIMATE and CIBERSORT algorithms. Predictive algorithms, including TIDE and IPS scores, were utilized to assess immunotherapy response. Immunohistochemistry analysis of Siglec15 and PD-L1 expression in clinical samples was performed. Additionally, cell culture experiments with SKOV3 cells and qRT-PCR assays were conducted to evaluate gene expression and functional effects of PD-L1 knockdown. Migration and invasion assays were carried out to assess cellular behaviors. RESULTS: Our study identified a novel prognostic subgroup in OC characterized by low Siglec15 and high PD-L1 expression, exhibiting improved overall survival compared to other subgroups. Further analysis revealed that the Siglec15low PD-L1high subgroup displayed a significantly more active immune microenvironment, characterized by increased infiltration of effector T cells, including CD8 T cells, activated memory CD4 T cells, and follicular helper T cells. This subgroup also showed upregulation of immune-related pathways, suggesting a more active immune response. Our results indicated that the Siglec15low PD-L1high subgroup is more likely to exhibit a favorable response to immunotherapy. Moreover, in vitro studies demonstrated that suppressing PD-L1 expression in OC cells led to increased Siglec15 expression and inhibited cell migration and invasion, suggesting a potential regulatory role of PD-L1 on Siglec15 expression and OC cells progression. CONCLUSIONS: Our findings emphasize the importance of combining assessment of Siglec15 and PD-L1 expression in patient stratification and treatment decision-making for OC, particularly regarding immunotherapy.