Oncology Department, Jinzhou Central Hospital, Jinzhou, China.
Department of Pediatrics, Jinzhou Central Hospital, Jinzhou, China.
Front Public Health. 2022 Jul 6;10:898270. doi: 10.3389/fpubh.2022.898270. eCollection 2022.
Although the role of hypoxia has been greatly explored and unveiled in glioblastoma (GBM), the mechanism of hypoxia-related long non-coding (lnc) RNAs has not been clearly understood. This study aims to reveal the crosstalk among hypoxia-related lncRNAs, tumor microenvironment (TME), and tumorigenesis for GBM. Gene expression profiles of GBM patients were used as a basis for identifying hypoxia-related lncRNAs. Unsupervised consensus clustering was conducted for classifying samples into different molecular subtypes. Gene set enrichment analysis (GSEA) was performed to analyze the enrichment of a series of genes or gene signatures. Three molecular subtypes were constructed based on eight identified hypoxia-related lncRNAs. Oncogenic pathways, such as epithelial mesenchymal transition (EMT), tumor necrosis factor-α (TNF-α) signaling, angiogenesis, hypoxia, P53 signaling, and glycolysis pathways, were significantly enriched in C1 subtype with poor overall survival. C1 subtype showed high immune infiltration and high expression of immune checkpoints. Furthermore, we identified 10 transcription factors (TFs) that were highly correlated with lncRNA-FAM66C. Three key lncRNAs (ADAMTS9-AS2, LINC00968, and LUCAT1) were screened as prognostic biomarkers for GBM. This study shed light on the important role of hypoxia-related lncRNAs for TME modulation and tumorigenesis in GBM. The eight identified hypoxia-related lncRNAs, especially FAM66C may serve as key regulators involving in hypoxia-related pathways.
尽管缺氧在胶质母细胞瘤（GBM）中的作用已经得到了广泛的探索和揭示，但缺氧相关长链非编码（lnc）RNAs 的机制尚未被清楚理解。本研究旨在揭示与缺氧相关的 lncRNAs、肿瘤微环境（TME）和肿瘤发生之间的相互作用，以研究 GBM。使用 GBM 患者的基因表达谱作为识别与缺氧相关的 lncRNAs 的基础。进行无监督共识聚类以将样本分类为不同的分子亚型。进行基因集富集分析（GSEA）以分析一系列基因或基因特征的富集。基于鉴定出的 8 个与缺氧相关的 lncRNA，构建了三个分子亚型。致癌途径，如上皮间充质转化（EMT）、肿瘤坏死因子-α（TNF-α）信号、血管生成、缺氧、P53 信号和糖酵解途径，在具有不良总体生存的 C1 亚型中显著富集。C1 亚型表现出高免疫浸润和高免疫检查点表达。此外，我们鉴定出与 lncRNA-FAM66C 高度相关的 10 个转录因子（TFs）。筛选出三个关键的 lncRNA（ADAMTS9-AS2、LINC00968 和 LUCAT1）作为 GBM 的预后生物标志物。本研究揭示了与缺氧相关的 lncRNAs 在调节 TME 和 GBM 肿瘤发生中的重要作用。鉴定出的 8 个与缺氧相关的 lncRNAs，尤其是 FAM66C，可能作为涉及缺氧相关途径的关键调节剂。
