Comprehensive analyses of m1A regulator-mediated modification patterns determining prognosis in lower-grade glioma (running title: m1A in LGG)

Kunjian Lei ^1,2,3, Yilei Sheng ^2,3,4, Min Luo ^1,5

⁰Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.

Heliyon +

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March 21, 2024

View abstract on PubMed

Summary

This study identifies a novel prognostic indicator for lower-grade gliomas (LGG) based on N1-methyladenosine (m1A) modification regulators. The developed m1A-related immune gene signature (m1A-RIGS) effectively predicts patient survival and informs potential immune-based therapies.

Area Of Science

Oncology
Molecular Biology
Immunology

Background

N1-methyladenosine (m1A) modification is a key post-transcriptional regulator of mRNA.
Research on m1A regulators in lower-grade gliomas (LGG) is limited.
Understanding m1A's role in LGG can reveal new therapeutic targets.

Purpose Of The Study

To investigate m1A regulators in LGG.
To develop a prognostic signature for LGG patients.
To explore potential therapeutic targets for LGG.

Main Methods

Nonnegative Matrix Factorization (NMF) applied to TCGA dataset to stratify LGG patients.
LASSO regression to identify m1A-related immune genes and establish m1A-RIGS.
Univariate/multivariate Cox regression and ssGSEA to validate prognostic and immune cell infiltration significance.
Edu assay and flow cytometry to assess the impact of MSR1 and BIRC5 modulation.

Main Results

NMF identified two LGG patient groups with distinct overall survival (OS) and immune cell infiltration.
The m1A-RIGS was established and demonstrated significant predictive value for LGG prognosis.
High- and low-risk subgroups showed significant variations in immune cell composition and function.
MSR1 and BIRC5 were identified as potential therapeutic targets, with their modulation affecting LGG cell behavior.

Conclusions

The m1A-RIGS serves as a robust prognostic indicator for LGG.
This signature may facilitate the development of novel immune-based treatment strategies for LGG.
BIRC5 and MSR1 represent promising therapeutic targets for LGG treatment.

Keywords:

Lower-grade glioma N1-methyladenosine Prognostic signature Tumor immune ssGSEA