The prognostic values of m6A RNA methylation regulators in uveal melanoma

Tang, Jing; Wan, Qi; Lu, Jianqun

doi:10.1186/s12885-020-07159-8

Cited by 34 publications

(25 citation statements)

References 30 publications

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“…Patients with high levels of mRNA methylation resulting from overexpression of reader proteins and methyltransferase complexes showed poor survival benefits in prostate cancer (Ji et al, 2020). In the subgroup construction signature of TCGA and GEO database, the m 6 A regulators showed a great value in malignant progression and prognosis of uveal melanoma (UM) (Tang et al, 2020). According to the clinical database of breast cancer of TCGA, RBM15B, YTHDF3, ZC3H13, METTL16, and LRPPRC were picked up indicating strong associations with clinical characteristics.…”

Section: Discussionmentioning

confidence: 99%

Expression and Prognostic Characteristics of m6 A RNA Methylation Regulators in Breast Cancer

Zhang

Jiang

2020

Front. Genet.

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PurposeN6-methyladenosine (m6A) is the most prevalent modification in mRNA methylation which has a wide effect on biological functions. This study aims to figure out the efficacy of m6A RNA methylation regulator-based biomarkers with prognostic significance in breast cancer.Patients and MethodsThe 23 RNA methylation regulators were firstly analyzed through ONCOMINE, then relative RNA-seq transcriptome and clinical data of 1,096 breast cancer samples and 112 normal tissue samples were acquired from The Cancer Gene Atlas (TCGA) database. The expressive distinction was also showed by the Gene Expression Omnibus (GEO) database. The gene expression data of m6A RNA regulators in human tissues were acquired from the Genotype-Tissue Expression (GTEx) database. The R v3.5.1 and other online tools such as STRING, bc-GeneExminer v4.5, Kaplan-Meier Plotter were applied for bioinformatics analysis.ResultsResults from ONCOMINE, TCGA, and GEO databases showed distinctive expression and clinical correlations of m6A RNA methylation regulators in breast cancer patients. The high expression of YTHDF3, ZC3H13, LRPPRC, and METTL16 indicated poor survival rate in patients with breast cancer, while high expression of RBM15B pointed to a better survival rate. Both univariate and multivariate Cox regression analyses revealed that age and risk scores were related to overall survival (OS). Univariate analysis also delineated that stage, tumor (T) status, lymph node (N) status, and metastasis (M) status were associated with OS. From another perspective, Kaplan-Meier Plotter platform showed that the relatively high expression of YTHDF3 and LRPPRC and the relatively low expression of RBM15B, ZC3H13, and METTL16 in breast cancer patients had worse Relapse-Free Survival (RFS). Breast Cancer Gene-Expression Miner v4.5 showed that LRPPRC level was negatively associated with ER and PR expression, while METTL16, RBM15B, ZC3H13 level was positively linked with ER and PR expression. In HER-2 (+) breast cancer patients, the expression of LRPPRC, METTL16, RBM15B, and ZC3H13 were all lower than the HER-2 (−) group.ConclusionThe significant difference in expression levels and prognostic value of m6A RNA methylation regulators were analyzed and validated in this study. This signature revealed the potential therapeutic value of m6A RNA methylation regulators in breast cancer.

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Section: Discussionmentioning

confidence: 99%

Expression and Prognostic Characteristics of m6 A RNA Methylation Regulators in Breast Cancer

Zhang

Jiang

2020

Front. Genet.

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“…To make the research more comprehensive, we selected 17 classical genes (METTL3, METTL14, WTAP, RBM15, ZC3H13, YTHDC1, YTHDC2, YTHDF1, YTHDF2, HNRNPC, FTO, ALKBH5, KIAA1429, IGF2BP1, IGF2BP2, IGF2BP3, and ELF3) as m 6 A RNA methylation regulators extracted from previous studies ( Luo et al, 2020 ; Tang et al, 2020 ). Gene expression were extracted from the TCGA-SCKM cohort and GTEx cutaneous group with corresponding clinical information.…”

Section: Methodsmentioning

confidence: 99%

Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous Melanoma

Feng

Wang

et al. 2021

Front. Mol. Biosci.

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Background: The purpose of our research was to establish a gene signature and determine the prognostic value of m6A methylation regulators in cutaneous melanoma and WTAP as a protective gene in cutaneous melanoma prognosis, we also evaluated gene mutations in cutaneous melanoma.Methods: We downloaded the RNA-seq transcriptome data and the clinical information for cutaneous melanoma patients from the GTEx and TCGA databases. Consensus clustering analysis was applied to divide the samples into two groups. Then the least absolute shrinkage and selection operator (LASSO) analyses were conducted to construct a risk signature, and we use external and internal datasets to verify its predictive value. We further searched the cBioPortal tools to detect genomic alterations and WTAP mutations. Finally, WTAP was further identified as a prognostic factor, and the related mechanisms mediated by WTAP were predicted by gene set enrichment analysis (GSEA). Experimental validations and have been further carried out.Results: Notably, m6A RNA methylation regulators play significant roles in tumorigenesis and development. In total, we selected three subtypes of cutaneous melanoma according to consensus clustering of the m6A RNA methylation regulators, and the stage of cutaneous melanoma was proven to be related to the subtypes. The Cox regression and LASSO analyses built a risk signature including ELF3, ZC3H13 and WTAP. The prognostic value of the risk signature in internal and external datasets have been proven then. The whole-genome and selected gene WTAP mutations were further explored. WTAP as a single prognostic factor was also explored and found to serve as an independent protective prognostic factor.Conclusions: Our study constructed a stable risk signature composed of m6A RNA methylation regulators in cutaneous melanoma. Moreover, WTAP was identified as a valuable prognostic factor and potential molecular target for cutaneous melanoma treatment.

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“…Using similar pipeline, many studies have revealed the diagnostic and prognostic roles of m 6 A or other methylation (e.g., m 1 A) regulators in specific cancer including but not limited to hepatocellular carcinoma [162] , [163] , uveal melanoma [164] , prostate cancer [165] , gynecological cancers [166] , esophageal cancer [167] , thyroid carcinoma [168] and renal carcinoma [169] . Moreover, Meng et al have built the m 6 A-related mRNA signature to predict the prognosis of pancreatic cancer patients [170] and predicted that PAH, ZPLD1, PPFIA3, and TNNT1 genes exhibited an independent prognostic value using correlation and survival analysis.…”

Section: Diagnosis and Prognosis Analysismentioning

confidence: 99%