The integrative analysis based on super-enhancer related genes for predicting different subtypes and prognosis of patient with lower-grade glioma

Yungang Hu; Qingqing Yang; Shuzhou Cai; Wei Wang; Shiyin Fu

doi:10.3389/fgene.2023.1085584

The integrative analysis based on super-enhancer related genes for predicting different subtypes and prognosis of patient with lower-grade glioma

Front Genet. 2023 Apr 7:14:1085584. doi: 10.3389/fgene.2023.1085584. eCollection 2023.

Authors

Yungang Hu¹, Qingqing Yang², Shuzhou Cai¹, Wei Wang¹, Shiyin Fu³

Affiliations

¹ Department of Neurosurgery, Wuhan University of Science and Technology Affiliated Xiaogan Central Hospital, Xiaogan, Hubei, China.
² Department of Thyroid and Breast Surgery, Wuhan University of Science and Technology Affiliated Xiaogan Central Hospital, Xiaogan, Hubei, China.
³ Department of Pediatric, Jinchu University of Technology Affiliated Central Hospital, Jingmen, Hubei, China.

Abstract

Objective: Emerging evidence revealed that super-enhancer plays a crucial role in the transcriptional reprogramming for many cancers. The purpose aimed to explored how the super-enhancer related genes affects the prognosis and tumor immune microenvironment (TIME) of patients with low-grade glioma (LGG). Methods: In this study, the differentially expressed genes (DEGs) between LGG cohorts and normal brain tissue cohort were identified by the comprehensive analysis of the super-enhancer (SE) related genes. Then non-negative matrix factorization was performed to seek the optimal classification based on the DEGs, while investigating prognostic and clinical differences between different subtypes. Subsequently, a prognostic related signature (SERS) was constructed for the comprehensive evaluation in term of individualized prognosis, clinical characteristics, cancer markers, genomic alterations, and immune microenvironment of patients with LGG. Results: Based on the expression profiles of 170 DEGs, we identified three SE subtypes, and the three subtypes showed significant differences in prognostic, clinicopathological features. Then, nine optimal SE-related genes were selected to construct the SERS through the least absolute shrinkage and selection operator Cox regression analysis. Survival analysis showed that SERS had strong and stable predictive ability for the prognosis of LGG patients in the The Cancer Genome Atlas, China Glioma Genome Atlas, and Remdrandt cohorts, respectively. We also found that SERS was highly correlated with clinicopathological features, tumor immune microenvironment, cancer hallmarks, and genomic alterations in LGG patients. In addition, the predictive power of SERS for immune checkpoint inhibitor treatment is also superior. The qRT-PCR results and immunohistochemical results also confirmed the difference in the expression of four key genes in normal cells and tumors, as well as in normal tissues and tumor tissues. Conclusion: The SERS could be suitable to utilize individualized prognosis prediction and immunotherapy options for LGG patients in clinical application.

Keywords: immunotherapy; lower-grade glioma; prognostic signature; super-enhancer; tumor immune microenvironment.