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ARTICLE

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

Bu Zou1,#, Yi-En Xu2,#, Hui-Chan He3, Zu-Lu Ye2, Da-Lei Zhou2, Cai-Yun He2,*, Chan Huang4,*
1 Department of Head and Neck, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
2 Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
3 Department of Blood Transfusion, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
4 Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
* Corresponding Author: Cai-Yun He. Email: email; Chan Huang. Email: email
# These authors contributed equally to this work as the first author
(This article belongs to the Special Issue: Novel Targets and Biomarkers in Solid Tumors)

Oncology Research https://doi.org/10.32604/or.2025.069453

Received 23 June 2025; Accepted 21 November 2025; Published online 29 December 2025

Abstract

Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

Keywords

Cluster of differentiation 73; gastric cancer; immune microenvironment; nomogram; phosphoinositide-3-kinase regulatory subunit 1

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