Identification and Validation of a Novel Three Hub Long Noncoding RNAs With m6A Modification Signature in Low-Grade Gliomas.

Quang-Huy Nguyen,Tin Nguyen,Duc-Hau Le

doi:10.3389/fmolb.2022.801931

Quang-Huy Nguyen, Tin Nguyen + Show 1 more

Open Access

https://doi.org/10.3389/fmolb.2022.801931

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Abstract

It has been evident that N6-methyladenosine (m6A)-modified long noncoding RNAs (m6A-lncRNAs) involves regulating tumorigenesis, invasion, and metastasis for various cancer types. In this study, we sought to pick computationally up a set of 13 hub m6A-lncRNAs in light of three state-of-the-art tools WGCNA, iWGCNA, and oCEM, and interrogated their prognostic values in brain low-grade gliomas (LGG). Of the 13 hub m6A-lncRNAs, we further detected three hub m6A-lncRNAs as independent prognostic risk factors, including HOXB-AS1, ELOA-AS1, and FLG-AS1. Then, the m6ALncSig model was built based on these three hub m6A-lncRNAs. Patients with LGG next were divided into two groups, high- and low-risk, based on the median m6ALncSig score. As predicted, the high-risk group was more significantly related to mortality. The prognostic signature of m6ALncSig was validated using internal and external cohorts. In summary, our work introduces a high-confidence prognostic prediction signature and paves the way for using m6A-lncRNAs in the signature as new targets for treatment of LGG.

Highlights

Gliomas are an umbrella term that includes the most common primary brain tumors of the central nervous system (CNS)
In the TCGA training cohort, 308 low-grade gliomas (LGG) patients alongside the 18 m6A-long non-coding RNAs (lncRNAs) became the input of the three co-expressed module identification tools, including weighted gene co-expression network analysis (WGCNA), improved version of WGCNA (iWGCNA), and variations of oCEM
Irrespective of the traditional treatment approaches of LGG we apply, LGG patients are still most likely to transform into this dangerous stage (Duffau and Taillandier, 2015)

Summary

Introduction

Gliomas are an umbrella term that includes the most common primary brain tumors of the central nervous system (CNS). According to their histopathological features, they are graded on a scale of I (the least malignant) to IV (the most malignant) by the World Health Organization (WHO) (Louis et al, 2007). Patients with brain low-grade gliomas (LGG) are assigned to the WHO grade II-III gliomas and said to have a rare cancer type of CNS. LGG is only held accountable for about 15% of all brain and CNS tumors (Lu et al, 2020). Unlike higher grade gliomas, LGG develops locally and slowly into the normal brain tissue instead of going outside the brain. It is a pressing need to detect LGG-related biomarkers for early recognition and diagnosis, and for development of individualized treatment approaches

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