5-Methylcytosine Related LncRNAs Reveal Immune Characteristics, Predict Prognosis and Oncology Treatment Outcome in Lower-Grade Gliomas

Abstract

5-Methylcytosine (m5C) methylation is an important RNA modification pattern that can participate in oncogenesis and progression of cancers by affecting RNA stability, expression of oncogenes, and the activity of cancer signaling pathways. Alterations in the expression pattern of long non-coding RNAs (lncRNAs) are potentially correlated with abnormalities in the m5C regulation features of cancers. Our aim was to reveal the mechanisms by which lncRNAs regulated the m5C process, to explore the impact of aberrant regulation of m5C on the biological properties of lower-grade gliomas (LGG), and to optimize current therapeutic. By searching 1017 LGG samples from the Cancer Genome Atlas and Chinese Glioma Genome Atlas, we first clarified the potential impact of m5C regulators on LGG prognosis in this study and used univariate Cox analysis and least absolute shrinkage and selection operator regression to explore clinically meaningful lncRNAs. Consequently, we identified four lncRNAs, including LINC00265, CIRBP-AS1, GDNF-AS1, and ZBTB20-AS4, and established a novel m5C-related lncRNAs signature (m5CrLS) that was effective in predicting prognosis. Notably, mutation rate, WHO class II, IDH mutation, 1p/19q co-deletion and MGMT promoter methylation were increased in the low m5CrLS score group. Patients with increased m5CrLS scores mostly showed activation of tumor malignancy-related pathways, increased immune infiltrating cells, and decreased anti-tumor immune function. Besides, the relatively high expression of immune checkpoints also revealed the immunosuppressed state of patients with high m5CrLS scores. In particular, m5CrLS stratification was sensitive to assess the efficacy of LGG to temozolomide and the responsiveness of immune checkpoint blockade. In conclusion, our results revealed the molecular basis of LGG, provided valuable clues for our understanding of m5C-related lncRNAs, and filled a gap between epigenetics and tumor microenvironment.

Keywords: 5-methylcytosine; immune; long non-coding RNAs; lower-grade gliomas; oncology treatment.