Department of Hyperbaric Oxygen, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
School of Biomedical Engineering, Beijing Key Laboratory of Fundamental Research on Biomechanics in Clinical Application, Capital Medical University, Beijing, 100069, China.
Curr Med Sci. 2024 Oct;44(5):1036-1046. doi: 10.1007/s11596-024-2934-7. Epub 2024 Oct 24.
The prognosis of glioblastoma is poor, and therapy-resistance is largely attributed to intratumor hypoxia. Hyperbaric oxygen (HBO) effectively alleviates hypoxia. However, the sole role of HBO in glioblastoma remains controversial. We previously reported that HBO can promote apoptosis, shorten protrusions, and delay growth of glioblastoma, but the molecular mechanism is unclear. We aimed to test candidate genes in HBO-exposed glioblastoma cells and to analyze their correlation with the survival of glioblastoma patients.
Glioblastoma cell lines exposed to repetitive HBO or normobaric air (NBA) were collected for RNA isolation and microarray data analysis. GO analysis, KEGG pathway analysis and survival analysis of the differentially expressed genes (DEGs) were performed.
HBO not only inhibited hypoxia-inducing genes including CA9, FGF11, PPFIA4, TCAF2 and SLC2A12, but also regulated vascularization by downregulating the expression of COL1A1, COL8A1, COL12A1, RHOJ and FILIP1L, ultimately attenuated hypoxic microenvironment of glioblastoma. HBO attenuated inflammatory microenvironment by reducing the expression of NLRP2, CARD8, MYD88 and CD180. HBO prevented metastasis by downregulating the expression of NTM, CXCL12, CXCL13, CXCR4, CXCR5, CDC42, IGFBP3, IGFBP5, GPC6, MMP19, ADAMTS1, EFEMP1, PTBP3, NF1 and PDCD1. HBO upregulated the expression of BAK1, PPIF, DDIT3, TP53I11 and FAS, whereas downregulated the expression of MDM4 and SIVA1, thus promoting apoptosis. HBO upregulated the expression of CDC25A, MCM2, PCNA, RFC33, DSCC1 and CDC14A, whereas downregulated the expression of ASNS, CDK6, CDKN1B, PTBP3 and MAD2L1, thus inhibiting cell cycle progression. Among these DEGs, 17 indicator-genes of HBO prolonging survival were detected.
HBO is beneficial for glioblastoma. Glioblastoma patients with these predictive indicators may prolong survival with HBO therapy. These potential therapeutic targets especially COL1A1, ADAMTS1 and PTBP3 deserve further validation.
胶质母细胞瘤的预后较差，而治疗耐药性在很大程度上归因于肿瘤内缺氧。高压氧（HBO）可有效缓解缺氧。然而，HBO 在胶质母细胞瘤中的唯一作用仍存在争议。我们之前的研究表明，HBO 可促进胶质母细胞瘤细胞凋亡、缩短突起并延缓生长，但分子机制尚不清楚。本研究旨在检测 HBO 暴露的胶质母细胞瘤细胞中的候选基因，并分析它们与胶质母细胞瘤患者生存的相关性。
收集重复 HBO 或常压空气（NBA）暴露的胶质母细胞瘤细胞系进行 RNA 分离和微阵列数据分析。对差异表达基因（DEGs）进行 GO 分析、KEGG 通路分析和生存分析。
HBO 不仅抑制了缺氧诱导基因，包括 CA9、FGF11、PPFIA4、TCAF2 和 SLC2A12，还通过下调 COL1A1、COL8A1、COL12A1、RHOJ 和 FILIP1L 的表达来调节血管生成，最终减轻了胶质母细胞瘤的缺氧微环境。HBO 通过降低 NLRP2、CARD8、MYD88 和 CD180 的表达来减轻炎症微环境。HBO 通过下调 NTM、CXCL12、CXCL13、CXCR4、CXCR5、CDC42、IGFBP3、IGFBP5、GPC6、MMP19、ADAMTS1、EFEMP1、PTBP3、NF1 和 PDCD1 的表达来防止转移。HBO 上调了 BAK1、PPIF、DDIT3、TP53I11 和 FAS 的表达，而下调了 MDM4 和 SIVA1 的表达，从而促进了细胞凋亡。HBO 上调了 CDC25A、MCM2、PCNA、RFC33、DSCC1 和 CDC14A 的表达，而下调了 ASNS、CDK6、CDKN1B、PTBP3 和 MAD2L1 的表达，从而抑制了细胞周期进程。在这些 DEGs 中，检测到了 17 个与 HBO 延长生存相关的指标基因。
HBO 对胶质母细胞瘤有益。具有这些预测指标的胶质母细胞瘤患者可能会通过 HBO 治疗延长生存。这些潜在的治疗靶点，特别是 COL1A1、ADAMTS1 和 PTBP3，值得进一步验证。
