» Articles » PMID: 34721523

N6-Methyladenosine-Related Long Non-coding RNA Signature Associated With Prognosis and Immunotherapeutic Efficacy of Clear-Cell Renal Cell Carcinoma

Overview
Journal Front Genet
Date 2021 Nov 1
PMID 34721523
Citations 7
Authors
Affiliations
Soon will be listed here.
Abstract

Increasing evidence suggests that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play important roles in cancer progression and immunotherapeutic efficacy in clear-cell renal cell carcinoma (ccRCC). In this study, we conducted a comprehensive ccRCC RNA-seq analysis using The Cancer Genome Atlas data to establish an m6A-related lncRNA prognostic signature (m6A-RLPS) for ccRCC. Forty-four prognostic m6A-related lncRNAs (m6A-RLs) were screened using Pearson correlation analysis (|R| > 0.7, < 0.001) and univariable Cox regression analysis ( < 0.01). Using consensus clustering, the patients were divided into two clusters with different overall survival (OS) rates and immune status according to the differential expression of the lncRNAs. Gene set enrichment analysis corroborated that the clusters were enriched in immune-related activities. Twelve prognostic m6A-RLs were selected and used to construct the m6A-RLPS through least absolute shrinkage and selection operator Cox regression. We validated the differential expression of the 12 lncRNAs between tumor and non-cancerous samples, and the expression levels of four m6A-RLs were further validated using Gene Expression Omnibus data and Lnc2Cancer 3.0 database. The m6A-RLPS was verified to be an independent and robust predictor of ccRCC prognosis using univariable and multivariable Cox regression analyses. A nomogram based on age, tumor grade, clinical stage, and m6A-RLPS was generated and showed high accuracy and reliability at predicting the OS of patients with ccRCC. The prognostic signature was found to be strongly correlated to tumor-infiltrating immune cells and immune checkpoint expression. In conclusion, we established a novel m6A-RLPS with a favorable prognostic value for patients with ccRCC. The 12 m6A-RLs included in the signature may provide new insights into the tumorigenesis and allow the prediction of the treatment response of ccRCC.

Citing Articles

A Narrative Review of Prognostic Gene Signatures in Oral Squamous Cell Carcinoma Using LASSO Cox Regression.

Mohd Faizal N, Shai S, Savaliya B, Karen-Ng L, Kumari R, Kumar R Biomedicines. 2025; 13(1).

PMID: 39857718 PMC: 11759772. DOI: 10.3390/biomedicines13010134.


Overview of the interplay between m6A methylation modification and non-coding RNA and their impact on tumor cells.

Dou Z, Ma X, Piao M, Wang J, Li J Transl Cancer Res. 2024; 13(6):3106-3125.

PMID: 38988908 PMC: 11231769. DOI: 10.21037/tcr-23-2401.


Elucidating the Influence of MPT-driven necrosis-linked LncRNAs on immunotherapy outcomes, sensitivity to chemotherapy, and mechanisms of cell death in clear cell renal carcinoma.

Huang J, Liu M, Chen H, Zhang J, Xie X, Jiang L Front Oncol. 2024; 13:1276715.

PMID: 38162499 PMC: 10757362. DOI: 10.3389/fonc.2023.1276715.


Selection of M7G-related lncRNAs in kidney renal clear cell carcinoma and their putative diagnostic and prognostic role.

Zhong S, Chen S, Lin H, Luo Y, He J BMC Urol. 2023; 23(1):186.

PMID: 37968670 PMC: 10652602. DOI: 10.1186/s12894-023-01357-9.


The lncRNA epigenetics: The significance of m6A and m5C lncRNA modifications in cancer.

Cusenza V, Tameni A, Neri A, Frazzi R Front Oncol. 2023; 13:1063636.

PMID: 36969033 PMC: 10033960. DOI: 10.3389/fonc.2023.1063636.


References
1.
Hinshaw D, Shevde L . The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res. 2019; 79(18):4557-4566. PMC: 6744958. DOI: 10.1158/0008-5472.CAN-18-3962. View

2.
Tian P, Wei J, Li J, Ren J, Yang J . LncRNA SNHG1 regulates immune escape of renal cell carcinoma by targeting miR-129-3p to activate STAT3 and PD-L1. Cell Biol Int. 2021; 45(7):1546-1560. DOI: 10.1002/cbin.11595. View

3.
Wanna-Udom S, Terashima M, Lyu H, Ishimura A, Takino T, Sakari M . The m6A methyltransferase METTL3 contributes to Transforming Growth Factor-beta-induced epithelial-mesenchymal transition of lung cancer cells through the regulation of JUNB. Biochem Biophys Res Commun. 2020; 524(1):150-155. DOI: 10.1016/j.bbrc.2020.01.042. View

4.
Yang X, Hu X, Liu J, Wang R, Zhang C, Han F . N6-methyladenine modification in noncoding RNAs and its function in cancer. Biomark Res. 2020; 8(1):61. PMC: 7653994. DOI: 10.1186/s40364-020-00244-x. View

5.
Liu J, Eckert M, Harada B, Liu S, Lu Z, Yu K . mA mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer. Nat Cell Biol. 2018; 20(9):1074-1083. PMC: 6245953. DOI: 10.1038/s41556-018-0174-4. View