Hypoxia-Related lncRNA Correlates With Prognosis and Immune Microenvironment in Lower-Grade Glioma

Front Immunol. 2021 Sep 30:12:731048. doi: 10.3389/fimmu.2021.731048. eCollection 2021.

Abstract

Background: Hypoxia-related genes are demonstrated to correlate with the prognosis of various cancers. However, the role of hypoxia-related long non-coding RNAs (HRLs) in lower-grade glioma (LGG) remains unclear.

Methods: A total of 700 LGG samples were extracted from TCGA and CGGA databases. Pearson correlation analysis was used to identify HRLs. Lasso analysis was adopted to construct the HRL signature. TIDE algorithm was used to predict responses to immune checkpoint inhibitors. Cell proliferation was estimated by cell counting kit-8 assay, colony formation assay, and EdU assay.

Results: We identified 340 HRLs and constructed a novel risk signature composed of 19 HRLs. The risk score exhibited potent value in predicting the prognosis of LGG patients and was significantly associated with the prognosis of LGG patients. Moreover, HRL signature could distinguish patients with similar expression levels of immune checkpoints and might predict the efficacy of immune checkpoint inhibitors. Additionally, hypoxia-related pathways and immune pathways were enriched in high-risk group, and high risk score indicated low tumor purity and high immune infiltration. Two major HRLs, LINC00941 and BASP1-AS1, could significantly affect the proliferation of glioma cells.

Conclusions: Our study constructed a novel HRL signature that could predict the prognosis and immunotherapy response of LGG patients. HRLs could be novel biomarkers to predict the prognosis of LGG patients and potential targets for LGG treatment.

Keywords: hypoxia; immune infiltration; immune microenvironment; long non-coding RNA; lower-grade glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / immunology
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Clinical Decision-Making
  • Databases, Genetic
  • Female
  • Gene Expression Profiling
  • Glioma / drug therapy
  • Glioma / genetics*
  • Glioma / immunology
  • Glioma / pathology
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Predictive Value of Tests
  • RNA, Long Noncoding / genetics*
  • Transcriptome
  • Tumor Hypoxia*
  • Tumor Microenvironment / immunology*

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • RNA, Long Noncoding