PIK3R1 as a Gastric Cancer Biomarker Linked to CD73⁺ Treg-Mediated Immunosuppression

Gastric cancer (GC) remains a major global health concern, and Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1), a regulatory subunit of the PI3K signaling pathway, may play a critical yet underexplored role in GC progression. This study aimed to investigate the prognostic significance of PIK3R1 in GC and its association with the tumor immune microenvironment.

PIK3R1 expression and its clinical relevance were analyzed using datasets from GC patients who underwent gastrectomy, including cohorts from The Cancer Genome Atlas (TCGA) and the Sun Yat-sen University Cancer Center (SYSUCC). Prognostic models integrating PIK3R1 expression with clinical parameters were constructed for both cohorts. The immune microenvironment associated with PIK3R1 expression was assessed through immunohistochemistry and single-cell RNA sequencing. In vitro assays were conducted to evaluate the effects of PIK3R1 on GC cell proliferation and migration.

PIK3R1 was significantly overexpressed in GC tissues and was closely associated with aggressive tumor characteristics and poor clinical outcomes. A nomogram combining PIK3R1 expression with clinicopathological features effectively predicted patient prognosis. Knockdown of PIK3R1 in GC cells reduced proliferation and migration in vitro. Immunological profiling revealed that high PIK3R1 expression correlated with increased infiltration of forkhead box protein P3 (Foxp3⁺) and cluster of differentiation 73 (CD73⁺) T cells. Patients with low PIK3R1 expression and low CD73⁺ T cell infiltration had significantly better survival.

PIK3R1 overexpression is linked to poor prognosis in GC and influences the extent of immune cell infiltration within the tumor microenvironment. A novel prognostic model integrating PIK3R1 and CD73 expression with clinical parameters was established to stratify GC patients into distinct risk groups, offering potential value for personalized therapeutic strategies.