ArticleWorld journal of surgical oncology2025
P2RX4 promotes hepatocellular carcinoma progression via calcium-mediated PI3K/AKT activation and immune remodeling.
Article in World journal of surgical oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Nucleotide signaling in neutrophils: a key player in cancer dynamics.Purinergic signalling · 2026Review
- Development and validation of nomograms integrating electrolyte, nutritional, and inflammatory indicators to predict survival in advanced esophageal cancer undergoing immunotherapy or radioimmunotherapy.Journal of thoracic disease · 2026Article
- Latest advances on the role of P2X Receptors in colorectal inflammation and cancer.Purinergic signalling · 2026Review
- High levels of P2RX5 expression predicts a poor prognosis and promotes tumor progression in endometrial cancer.International journal of clinical and experimental pathology · 2026Article
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5 authors.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is frequently identified at advanced stages. This constrains therapeutic options and results in poor prognosis. P2RX4 is an ATP-gated ion channel that modulates calcium influx. It participates in cellular proliferation, inflammatory processes, and immunological reactions. Nonetheless, its role in HCC remains poorly comprehended. This study explored the expression, function, and immunological effects of P2RX4 in HCC.
methodsWe examined P2RX4 expression using TCGA-LIHC and TIMER2.0 databases. Protein levels were validated using immunohistochemistry in 140 HCC tissues. A prognostic model was developed utilising P2RX4 expression. In vitro investigations were conducted subsequent to the silencing of P2RX4. The experiments encompassed cell proliferation, invasion, and colony formation. We further conducted transcriptome sequencing. Ion concentrations were quantified with ICP-OES. PI3K/AKT activation was evaluated using Western blotting.
resultsP2RX4 exhibited elevated expression in HCC tissues. Its expression was associated with advanced tumor stage and poor prognosis. Silencing of P2RX4 decreased tumour cell proliferation and invasion. It also reduced intracellular calcium levels and inhibited AKT phosphorylation. Elevated P2RX4 levels correlated with an increased presence of M0 macrophages and Tregs, a reduced number of monocytes, and a poorer anticipated response to immunotherapy.
conclusionsP2RX4 may facilitate HCC progression by augmenting calcium influx, activating the PI3K/AKT pathway, and diminishing anti-tumor immunity. It may function as a biomarker and therapeutic target in HCC. Additional, in vivo investigations are required to validate these findings.
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