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AIMS: Hypoxia reduces tumour radiosensitivity and hypoxia inducible factor-1alpha (HIF-1alpha) plays an important role in this process. The aim of the study was to assess the prognostic impact of HIF-1alpha and vascular endothelial growth factor (VEGF) in patients with nasopharyngeal carcinoma who received radiation with hypoxia-modifying therapy (carbogen plus nicotinamide). MATERIALS AND METHODS: The immunohistochemical expression of HIF-1alpha and VEGF was evaluated in nasopharyngeal carcinoma biopsies from 59 patients who received conventional radiotherapy combined with carbogen and nicotinamide. RESULTS: A significant positive association was found between HIF-1alpha and VEGF expression (P=0.003). There was no association found between the level of HIF-1alpha, VEGF expression and tumour stage, nodal stage, or clinical stage. Kaplan-Meier plots showed that positive HIF-1alpha and VEGF expression were associated with a higher distant metastasis, a worse overall and disease-free survival, and the level of HIF-1alpha and VEGF expression had no effect on locoregional recurrence. The multivariate analysis failed to confirm any association between HIF-1alpha or VEGF and metastasis, disease-free or overall survival. CONCLUSIONS: These results suggest that the expression of hypoxia-associated markers (HIF-1alpha and VEGF) may have prognostic significance in patients with nasopharyngeal carcinoma who receive radiation plus carbogen and nicotinamide, but further study is needed. [ABSTRACT FROM AUTHOR]

Ischemic stroke and vascular dementia, as common cerebrovascular diseases, with the former causing irreversible neurological damage and the latter causing cognitive and memory impairment, are closely related and have long received widespread attention. Currently, the potential causative genes of these two diseases have yet to be investigated, and effective early diagnostic tools for the diseases have not yet emerged. In this study, we screened new potential biomarkers and analyzed new therapeutic targets for both diseases from the perspective of immune infiltration. Two gene expression profiles on ischemic stroke and vascular dementia were obtained from the NCBI GEO database, and key genes were identified by LASSO regression and SVM-RFE algorithms, and key genes were analyzed by GO and KEGG enrichment. The CIBERSORT algorithm was applied to the gene expression profile species of the two diseases to quantify the 24 subpopulations of immune cells. Moreover, logistic regression modeling analysis was applied to illustrate the stability of the key genes in the diagnosis. Finally, the key genes were validated using RT-PCR assay. A total of 105 intersecting DEGs genes were obtained in the 2 sets of GEO datasets, and bioinformatics functional analysis of the intersecting DEGs genes showed that GO was mainly involved in the purine ribonucleoside triphosphate metabolic process，respiratory chain complex，DNA-binding transcription factor binding and active transmembrane transporter activity. KEGG is mainly involved in the Oxidative phosphorylation, cAMP signaling pathway. The LASSO regression algorithm and SVM-RFE algorithm finally obtained three genes, GAS2L1, ARHGEF40 and PFKFB3, and the logistic regression prediction model determined that the three genes, GAS2L1 (AUC: 0.882), ARHGEF40 (AUC: 0.867) and PFKFB3 (AUC: 0.869), had good diagnostic performance. Meanwhile, the two disease core genes and immune infiltration were closely related, GAS2L1 and PFKFB3 had the highest positive correlation with macrophage M1 (p < 0.001) and the highest negative correlation with mast cell activation (p = 0.0017); ARHGEF40 had the highest positive correlation with macrophage M1 and B cells naive (p < 0.001), the highest negative correlation with B cell memory highest correlation (p = 0.0047). RT-PCR results showed that the relative mRNA expression levels of GAS2L1, ARHGEF40, and PFKFB3 were significantly elevated in the populations of both disease groups (p < 0.05). Immune infiltration-based models can be used to predict the diagnosis of patients with ischemic stroke and vascular dementia and provide a new perspective on the early diagnosis and treatment of both diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)