AUTHOR=Teng Chubei , Zhu Yongwei , Li Yueshuo , Dai Luohuan , Pan Zhouyang , Wanggou Siyi , Li Xuejun 

TITLE=Recurrence- and Malignant Progression-Associated Biomarkers in Low-Grade Gliomas and Their Roles in Immunotherapy

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.899710

DOI=10.3389/fimmu.2022.899710

ISSN=1664-3224

ABSTRACT=Despite a generally better prognosis than HGG, recurrence and malignant progression are the main causes for the poor prognosis and difficulties in the treatment of LGG. It is of great importance to learn about the risk factors and underlying mechanisms of LGG recurrence and progression. In this study, the transcriptome characteristics of four groups, namely, normal brain tissue and rLGG, normal brain tissue and sGBM, pLGG and rLGG, and pLGG and sGBM, were compared using CGGA and GTEx databases. 296 down-regulated and 396 up-regulated DEGs with high consensus were screened out. Univariate Cox regression analysis of data from TCGA yielded 86 prognostically relevant DEGs, a prognostic prediction model based on five key genes (HOXA1, KIF18A, FAM133A, HGF, and MN1) were established using LASSO regression dimensionality reduction and multivariate Cox regression analysis. LGG was divided into high- and low-risk groups using this prediction model, GSEA analysis revealed that signaling pathway differences in the high- and low-risk groups were mainly seen in tumor immune regulation and DNA damage-related cell cycle checkpoints. Furthermore, the infiltration of immune cells in the high- and low-risk groups were analyzed, which indicated a stronger infiltration of immune cells in the high-risk group than that in the low-risk group, suggesting that an immune microenvironment more conducive to tumor growth emerged due to the interaction between tumor and immune cells. The tumor mutation burden and methylation burden in the high and low-risk groups were also analyzed, which indicated higher gene mutation burden and lower DNA methylation level in the high-risk group, suggesting that with the accumulation of genomic mutations and epigenetic changes, tumor cells continued to evolve and led to the progression of LGG to HGG. Finally, the value of potential therapeutic targets for five key genes was analyzed, and the findings demonstrated that KIF18A was the gene most likely to be a potential therapeutic target. In conclusion, the prediction model based on these five key genes can better identify the high- and low-risk groups of LGG and lay a solid foundation for evaluating the risk of LGG recurrence and malignant progression.