Image1_The Role of m6A RNA Methylation-Related lncRNAs in the Prognosis and Tumor Immune Microenvironment of Papillary Thyroid Carcinoma.PNG
Emerging evidence has indicated that N6-methylandenosine (m6A) RNA methylation plays a critical role in cancer development. However, the function of m6A RNA methylation-related long noncoding RNAs (m6A-lncRNAs) in papillary thyroid carcinoma (PTC) has never been reported. This study aimed to investigate the role of m6A-lncRNAs in the prognosis and tumor microenvironment (TME) of PTC. Three subgroups (clusters 1, 2, and 3) were identified by consensus clustering of 19 prognosis-related m6A-lncRNA regulators, of which cluster 1 is preferentially related to unfavorable prognosis, lower immune scores, and distinct immune infiltrate level. A risk-score model was established based on 8 prognosis-related m6A-lncRNAs. Patients with a high-risk score showed a worse prognosis, and the ROC indicated a reliable prediction performance for patients with PTC (AUC = 0.802). As expected, the immune scores, the infiltration levels of immune cells, and ESTIMATE scores in the low-risk subgroups were notably higher (p < 0.001) when compared with those in high-risk subgroups. Furthermore, GSEA analysis revealed that tumor associated pathways, hallmarks, and biological processes were remarkably enriched in the high-risk subgroup. Further analysis indicated that the risk score and age were independent prognostic factors for PTC. An integrated nomogram was constructed that accurately predicted the survival status (AUC = 0.963). Moreover, a lncRNA–miRNA–mRNA regulated network was established based on seven prognosis-related m6A-lncRNAs. In addition, 30 clinical samples and different PTC cells were validated. This is the first study to reveal that m6A-lncRNAs plays a vital role in the prognosis and TME of PTC. To a certain degree, m6A-lncRNAs can be considered as new, promising prognostic biomarkers and treatment targets.
History
References
- https://doi.org//10.1002/hep.29683
- https://doi.org//10.1002/cam4.2046
- https://doi.org//10.3892/etm.2013.933
- https://doi.org//10.1186/s10020-020-00185-z
- https://doi.org//10.1089/thy.2018.0186
- https://doi.org//10.3389/fonc.2020.578963
- https://doi.org//10.7150/jca.40866
- https://doi.org//10.15252/embr.201949229
- https://doi.org//10.1038/s41419-020-2674-y
- https://doi.org//10.1089/thy.2015.0020
- https://doi.org//10.1186/s12943-019-1109-9
- https://doi.org//10.1038/s41417-020-00208-1
- https://doi.org//10.1038/s41418-019-0461-z
- https://doi.org//10.1042/BSR20193489
- https://doi.org//10.1634/theoncologist.2020-0449
- https://doi.org//10.1111/jcmm.15193
- https://doi.org//10.1093/nar/gkv1070
- https://doi.org//10.1371/journal.pgen.1007412
- https://doi.org//10.1016/j.ccell.2020.09.004
- https://doi.org//10.1002/jcp.27587
- https://doi.org//10.1002/iub.2365
- https://doi.org//10.1093/nar/gkaa407
- https://doi.org//10.2147/NDT.S305182
- https://doi.org//10.1001/jama.2017.2719
- https://doi.org//10.1186/s13046-018-0950-9
- https://doi.org//10.4048/jbc.2021.24.e32
- https://doi.org//10.1186/s13045-019-0805-7
- https://doi.org//10.1038/ng1180
- https://doi.org//10.1096/fj.202000762R
- https://doi.org//10.3390/cancers13040648
- https://doi.org//10.1097/01.mnm.0000126625.17166.36
- https://doi.org//10.1016/j.molmet.2021.101209
- https://doi.org//10.1038/s41590-020-0650-4
- https://doi.org//10.1073/pnas.0506580102
- https://doi.org//10.1210/clinem/dgaa545
- https://doi.org//10.1089/thy.2020.0330
- https://doi.org//10.1089/dna.2020.5956
- https://doi.org//10.3389/fcell.2020.00642
- https://doi.org//10.1186/s12943-017-0680-1
- https://doi.org//10.3389/fonc.2020.00003
- https://doi.org//10.1186/s12943-020-01204-7
- https://doi.org//10.21037/atm-21-383
- https://doi.org//10.1186/s12957-020-01948-y
- https://doi.org//10.1186/s12935-021-01939-3
- https://doi.org//10.1016/j.molcel.2018.02.015
- https://doi.org//10.1186/s12943-020-01293-4
- https://doi.org//10.1093/bioinformatics/btq170
- https://doi.org//10.1159/000494786
- https://doi.org//10.3389/fendo.2020.570604
- https://doi.org//10.7150/jca.41193
- https://doi.org//10.1186/s13046-020-01714-8
- https://doi.org//10.1016/j.omtn.2020.09.023
- https://doi.org//10.1186/s12943-020-01233-2
- https://doi.org//10.1038/ncomms3612
- https://doi.org//10.18388/abp.2020_5454
- https://doi.org//10.3389/fmed.2020.00556
- https://doi.org//10.1016/j.ccell.2017.02.013
- https://doi.org//10.3389/fonc.2020.540238
- https://doi.org//10.1186/s13045-020-00872-8
- https://doi.org//10.1186/s12943-020-01216-3