Constructing anoikis-related signatures in glioma and identifying PLAU as a new prognostic biomarker

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BACKGROUND: Glioma, the most common aggressive tumor found in the central nervous system, is linked to a poor prognosis. Anoikis is a form of cell death that arises from the detachment of cells. Disruption of the anoikis pathway can facilitate the survival and dispersal of cancer cells from the primary tumor site, thus playing a critical role in the spread and advancement of cancer. The process of Epithelial-to-mesenchymal transition (EMT) is crucial in the progression and spread of cancer, where epithelial cells undergo a loss of polarity and adhesion, transitioning into mesenchymal cells with heightened capability for invasion and metastasis. However, there is a dearth of research examining the mechanism of anoikis and its correlation with the EMT process in glioma. METHODS: In our study, data was extracted from 1317 samples of glioma for comparative examination. Through the utilization of 28 genes associated with resistance to cell detachment, we aimed to distinguish various categories of glioma patients by evaluating the immune environment and pathways of enrichment within the two subgroups. By implementing diverse statistical methodologies such as COX regression analysis and the least absolute shrinkage and selection operator regression, we developed a risk scoring system to categorize glioma patients into cohorts of high and low risk. The clinical features, infiltration of immune cells, and responsiveness to drugs were thoroughly investigated for both categories, highlighting distinctions across various domains. Moreover, our investigation encompassed in vitro trials to assess the function and expression of the pivotal gene, PLAU. RESULTS: The differences in prognoses, immune status, and drug sensitivities between high-risk and low-risk groups highlight the need for personalized treatment approaches in glioma patients. By integrating risk scores with clinicopathological characteristics, a nomogram was created to better predict patient outcomes and guide treatment decisions. The nomogram demonstrated its usefulness through decision curve analysis, showing potential benefits for enhancing clinical strategies in glioma management. In cell experiments, targeting Plasminogen activator urokinase (PLAU)led to a notable decrease in the growth, spread, and movement abilities of T98G and U251 cell lines, as well as blocking the epithelial-mesenchymal transition process. CONCLUSION: The study we conducted establishes the groundwork for comprehending the function of anoikis genes in glioma, and recognizes PLAU as a potential biomarker for glioma.

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