ArticleFrontiers in immunology2025
The osteosarcoma immune microenvironment in progression: PLEK as a prognostic biomarker and therapeutic target.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed.
- NFS1 activates PI3K/AKT/mTOR signaling to upregulate GPX4 expression and enhance ferroptosis resistance in osteosarcoma.Functional & integrative genomics · 2026Article
- Review
- Metabolic-immune crosstalk in osteosarcoma: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Nutritional biomarkers regulating tumor immune microenvironment in osteosarcoma and as predictors of immune checkpoint inhibitor responses.Frontiers in immunology · 2026Review
- Advances in T cell-based immunotherapy for osteosarcoma.Frontiers in immunology · 2026Review
- NGF/BDNF-Trk/p75NTR signaling in osteosarcoma immunity: biomarkers and therapeutic opportunities.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Osteosarcoma (OS) is a malignant bone tumor with high metastatic potential and poor long-term survival. The tumor immune microenvironment and metabolic reprogramming are increasingly recognized as key drivers of OS progression, yet the molecular links between these systems remain unclear. This study aimed to identify immune-metabolic biomarkers in OS, focusing on pleckstrin (PLEK) as a potential regulatory hub. Methods: We conducted differential expression and survival analyses using OS transcriptomic datasets and TCGA/GTEx data. Protein-protein interaction networks, GO/KEGG enrichment, and CytoHubba algorithms identified core hub genes. Tumor-infiltrating immune cells were profiled via TIMER. Single-cell RNA-seq (GSE162454) was used for immune and metabolic landscape mapping. PLEK was further validated by qRT-PCR and Western blot in OS samples, and its function assessed via siRNA knockdown in macrophages within TME co-cultured with OS cells. Cell proliferation, migration, and invasion assays evaluated phenotypic effects in OS cells. Results: Nine hub genes were identified, with PLEK significantly upregulated in OS tissues. High PLEK expression correlated with improved survival and increased infiltration of macrophages, dendritic cells, and CD4 Discussion: Our study identifies PLEK as a prognostic biomarker and functional regulator in OS. It promotes an immune-infiltrated, metabolically active tumor microenvironment and is associated with attenuated malignant phenotypes
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.