Biomedicines · Published 2026-08-01 · DOI 10.3390/biomedicines14081738
Shiyun Peng, Zhenkun Wen, Xiao-Ting Cai
<b>Background/Objectives:</b> Glioblastoma (GBM) is widely recognised as a highly aggressive form of malignant tumour arising within the central nervous system. The proneural-to-mesenchymal (PN–MES) state transition is a key process underlying malignant progression and therapeutic resistance. The present study was designed to elucidate the association between the PN–MES transition and arachidonic acid (AA) metabolic reprogramming in GBM. <b>Methods:</b> We integrated four public single-cell RNA-sequencing cohorts, two spatial transcriptomic cohorts, and three bulk RNA-sequencing cohorts for GBM. By combining single-cell transcriptomics, spatial transcriptomics, pseudotime trajectory inference, and cell–cell communication analysis, we systematically evaluated the cell-state dependence and spatial heterogeneity of AA metabolism in GBM. We further incorporated machine learning-based survival modelling, molecular docking, molecular dynamics simulations, and in vitro functional assays to identify and validate potential prognostic biomarkers and therapeutic targets. <b>Results:</b> Mesenchymal-like (MES-like) tumour cells showed the highest transcriptionally inferred AA metabolism-related score, and AA metabolism-related gene expression was closely coupled with PN–MES state transition. The peptidylprolyl isomerase A (<i>PPIA</i>)–basigin (<i>BSG</i>) signalling axis was selectively enriched in tumour cells with high expression of arachidonic acid metabolism-related genes (AAMGs), whereas virtual knockout of <i>BSG</i> perturbed MES- and invasion-related gene modules. Spatial transcriptomic analysis confirmed that <i>PPIA</i>–<i>BSG</i>-associated communication was enhanced within MES-like tumour niches and was coupled with inflammatory and hypoxic programmes. AA metabolism-related genes enabled robust prognostic stratification. Molecular simulation and in vitro experiments suggested that Venetoclax could bind <i>BSG</i> and suppress GBM cell viability. <b>Conclusions:</b> AA metabolism-related transcriptional reprogramming defines mesenchymal-associated malignant niches in GBM and may contribute to PN–MES-related state evolution through <i>PPIA</i>–<i>BSG</i>-mediated microenvironmental communication. AA metabolism-related features and the <i>BSG</i>-associated signalling axis may provide candidate directions for prognostic stratification and targeted intervention.
Abstract from DOAJ. Public domain (CC0 1.0).
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Peng, S., Wen, Z., Cai, X. (2026). Integrative Single-Cell and Spatial Transcriptomic Analyses Link Arachidonic Acid Metabolic Reprogramming to Proneural-to-Mesenchymal State Transition in Glioblastoma. Biomedicines. https://doi.org/10.3390/biomedicines14081738