Abstract
BackgroundMETTL14, as one of N6-methyladenosine (m6A) related genes, has been found to be associated with promoting tumorigenesis in different types of cancers. This study was aimed to investigate the prognostic value of METTL14 in clear cell renal cell carcinoma (ccRCC).MethodsWe collected ccRCC patients’ clinicopathological parameters information and 13 m6A related genes expression from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were conducted to investigate whether METTL14 could serve as an independent factor correlated with overall survival (OS). Gene Set Enrichment Analysis (GSEA) was carried out to identify METTL14-related signaling pathways. Moreover, a risk score (RS) was calculated to predict the prognosis of ccRCC. Quantitative real-time PCR (qRT-PCR) was also utilized to verify the expression of METTL14 in clinical specimens.ResultsDifferently expressed m6A related genes were identified between ccRCC tissues and normal tissues. Therein, METTL14 was lowly expressed in ccRCC tissues and verified by qRT-PCR (all p < 0.01). Survival analysis indicated that high expression of METTL14 was associated with better OS (p = 1e−05). GSEA results revealed that high METTL14 expression was enriched in ERBB pathway, MAPK pathway, mTOR pathway, TGF-β pathway and Wnt pathway. Moreover, METTL14 was proved to be an independent prognostic factor by means of univariate and multivariate Cox regression analyses. Nomogram integrating both the METTL14 expression and clinicopathologic variables was also established to provide clinicians with a quantitative approach for predicting survival probabilities of ccRCC. Furthermore, a METTL14-based riskscore (RS) was developed with significant OS (p = 6.661e−16) and increased AUC of 0.856. Besides, significant correlated genes with METTL14 were also provided.ConclusionsOur results indicated that METTL14 could serve as a favorable prognostic factor for ccRCC. Moreover, this study also provided a prognostic signature to predict prognosis of ccRCC and identified METTL14-related signaling pathways.
Highlights
METTL14, as one of N6-methyladenosine (m6A) related genes, has been found to be associated with promoting tumorigenesis in different types of cancers
The results indicated that high METTL3 expression was associated with some essential signaling pathways including ERBB pathway, MAPK pathway, mTOR pathway, renal cell carcinoma, pathway in cancer, TGF-β pathway and Wnt pathway (Fig. 5 and Table 3), giving a clue of the underlying mechanism in the pathogenesis of clear cell renal cell carcinoma (ccRCC)
Our results discovered that high METTL14 expression had association with ERBB pathway, MAPK pathway, mTOR pathway, renal cell carcinoma, TGF-β pathway and Wnt pathway by Gene Set Enrichment Analysis (GSEA)
Summary
METTL14, as one of N6-methyladenosine (m6A) related genes, has been found to be associated with promoting tumorigenesis in different types of cancers. Clear cell renal cell carcinoma (ccRCC), as the most common histological type of RCC, accounts for approximately 85% of all primary renal neoplasms [2]. As the most common type of mRNA modification in eukaryote, m6A was proved to be highly conserved, as well as in human and mouse. RNA m6A modification has been shown to play vital for RNA splicing, export, stability, regulation of RNA-protein interaction and gene expression [4, 8,9,10]. The genes of “writers” compose a mRNA methyltransferase enzyme complex, including METTLE3, METTL14, WTAP, KIAA1429, ZC3H13 and RBM15, while the reversible process is catalysed by m6A “erasers”, FTO and ALKBH5, conducting demethylation of m6A. In order to exert functions of m6A modifications, mRNA m6A sites can be recognized by RNA-binding proteins “readers”, including YTHDF1, YTHDF2, YTHDC1, YTHDC2 and HNRNPC
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