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.

Ring finger protein 145 (RNF145), an E3 ubiquitin ligase, is significantly upregulated in hepatocellular carcinoma (HCC). However, its role in HCC remains unknown. The study aimed to investigate the functions and underlying mechanisms of RNF145 in HCC.

The role of RNF145 in HCC was investigated using data from The Cancer Genome Atlas (TCGA) and in vitro experimental assays. Its oncogenic functions were assessed using the transwell migration assay and the wound-healing assay. The molecular mechanism was explored through protein immunoprecipitation and western blot analyses. Data from public databases were analyzed to correlate RNF145 expression with clinicopathological features. Univariate and multivariate Cox analyses established RNF145 as an independent prognostic factor. Subsequently, a prognostic nomogram was constructed.

RNF145 was upregulated in HCC. The expression level of RNF145 in HCC showed significant correlations with histological grade, pathological stage, and vascular invasion. Functionally, knockdown of RNF145 effectively abolished the migratory and invasive capacities of HCC cells. This pro-metastatic effect is mediated through the RNF145-driven ubiquitination and subsequent degradation of protocadherin 9 (PCDH9).

Our findings confirm the significant upregulation of RNF145 in HCC and promote metastasis by facilitating PCDH9 ubiquitination and degradation, highlighting its role as a prognostic biomarker and a potential therapeutic target.