Identification of a methyltransferase-related long noncoding RNA signature as a novel prognosis biomarker for lung adenocarcinoma

May 21, 2024Aging

Long noncoding RNA related to methyltransferase as a new marker to predict lung adenocarcinoma outcomes

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

A set of 32 methyltransferase-related long non-coding RNAs (MeRlncRNAs) was identified in lung adenocarcinoma (LUAD).

Six prognostic lncRNAs were selected to develop gene signatures for LUAD risk assessment.
The risk score derived from these signatures acted as an independent prognostic factor associated with immune-related pathways.
High-risk groups exhibited a suppressed immune landscape, which may contribute to poorer prognoses.
A regulatory network was constructed, including 6 prognostic lncRNAs, 19 microRNAs, and 21 messenger RNAs.
Confirmatory tests using RT-qPCR validated the expression of these prognostic lncRNAs in both normal and LUAD samples.

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BACKGROUND: Lung adenocarcinoma (LUAD) accounts for a high proportion of tumor deaths globally, while methyltransferase-related lncRNAs in LUAD were poorly studied.

METHODS: In our study, we focused on two distinct cohorts, TCGA-LUAD and GSE3021, to establish a signature of methyltransferase-related long non-coding RNAs (MeRlncRNAs) in LUAD. We employed univariate Cox and LASSO regression analyses as our main analytical tools. The GSE30219 cohort served as the validation cohort for our findings. Furthermore, to explore the differential pathway enrichments between groups stratified by risk, we utilized Gene Set Enrichment Analysis (GSEA). Additionally, single-sample GSEA (ssGSEA) was conducted to assess the immune infiltration landscape within each sample. Reverse transcription quantitative PCR (RT-qPCR) was also performed to verify the expression of prognostic lncRNAs in both clinically normal and LUAD samples.

RESULTS: In LUAD, we identified a set of 32 MeRlncRNAs. We further narrowed our focus to six prognostic lncRNAs to develop gene signatures. The TCGA-LUAD cohort and GSE30219 were utilized to validate the risk score model derived from these signatures. Our analysis showed that the risk score served as an independent prognostic factor, linked to immune-related pathways. Additionally, the analysis of immune infiltration revealed that the immune landscape in high-risk groups was suppressed, which could contribute to poorer prognoses. We also constructed a regulatory network comprising 6 prognostic lncRNAs, 19 miRNAs, and 21 mRNAs. Confirmatory RT-qPCR results aligned with public database findings, verifying the expression of these prognostic lncRNAs in the samples.

CONCLUSION: The prognostic gene signature of LUAD associated with MeRlncRNAs that we provided, may offer us a comprehensive picture of the prognosis prediction for LUAD patients.

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Identification of a methyltransferase-related long noncoding RNA signature as a novel prognosis biomarker for lung adenocarcinoma

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