Author:
Feng Rui,Li Haolin,Meng Tong,Fei Mingtian,Yang Cheng
Abstract
Abstract
Purpose
This study aimed to construct an m6A and cuproptosis-related long non-coding RNAs (lncRNAs) signature to accurately predict the prognosis of kidney clear cell carcinoma (KIRC) patients using the information acquired from The Cancer Genome Atlas (TCGA) database.
Methods
First, the co-expression analysis was performed to identify lncRNAs linked with N6-methyladenosine (m6A) and cuproptosis in ccRCC. Then, a model encompassing four candidate lncRNAs was constructed via univariate, least absolute shrinkage together with selection operator (LASSO), and multivariate regression analyses. Furthermore, Kaplan–Meier, principal component, functional enrichment annotation, and nomogram analyses were performed to develop a risk model that could effectively assess medical outcomes for ccRCC cases. Moreover, the cellular function of NFE4 in Caki-1/OS-RC-2 cultures was elucidated through CCK-8/EdU assessments and Transwell experiments. Dataset outcomes indicated that NFE4 can have possible implications in m6A and cuproptosis, and may promote ccRCC progression.
Results
We constructed a panel of m6A and cuproptosis-related lncRNAs to construct a prognostic prediction model. The Kaplan–Meier and ROC curves showed that the feature had acceptable predictive validity in the TCGA training, test, and complete groups. Furthermore, the m6A and cuproptosis-related lncRNA model indicated higher diagnostic efficiency than other clinical features. Moreover, the NFE4 function analysis indicated a gene associated with m6A and cuproptosis-related lncRNAs in ccRCC. It was also revealed that the proliferation and migration of Caki-1 /OS-RC-2 cells were inhibited in the NFE4 knockdown group.
Conclusion
Overall, this study indicated that NFE4 and our constructed risk signature could predict outcomes and have potential clinical value.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Reference58 articles.
1. Garje R, Elhag D, Yasin HA, et al. Comprehensive review of chromophobe renal cell carcinoma. Crit Rev Oncol Hematol. 2021;160: 103287.
2. Bian Z, Fan R, Xie L. A novel cuproptosis-related prognostic gene signature and validation of differential expression in clear cell renal cell carcinoma. J Genes (Basel). 2022;13(5):851.
3. Bahadoram S, Davoodi M, Hassanzadeh S, et al. Renal cell carcinoma: an overview of the epidemiology, diagnosis, and treatment. J G Ital Nefrol. 2022;39(3):1.
4. Stoccoro A, Coppedè F. Mitochondrial DNA methylation and human diseases. Int J Mol Sci. 2021;22(9):4594.
5. Liu N, Pan T. N6-methyladenosine–encoded epitranscriptomics. Nat Struct Mol Biol. 2016;23(2):98–102.