Abstract
BackgroundRibosomal RNA N6-methyltransferase METTL5 was reported to catalyze m6A in 18S rRNA. We aimed to investigate the expression and prognostic features of METTL5 in gastric cancer (GC).MethodsIn this study, 168 GC patients and their corresponding adjacent tissues were collected. Immunohistochemical staining was used to detect the expression of METTL5 protein. Univariate and multivariate Cox analysis were used to dertermine the prognostic role of METTL5 protein in GC, and a nomogram was constructed to evaluate GC patients’ prognosis based on METTL5 expression. Data from TCGA and GEO database were also used to validate the prognostic value of METTL5 in GC patients on mRNA level. We further performed GSEA enrichment analysis to explore the possible function and related pathways related to METTL5.ResultsMETTL5 protein in gastric cancer tissues (GCTs) was significantly decreased compared with adjacent normal tissues (ANTs) and adjacent intestinal metaplasia tissues (AIMTs) (P < 0.001, respectively). Meanwhile, METTL5 expression was negatively correlated with clinicopathologic stage. According to multivariate Cox proportional hazards model analysis, METTL5 protein expression was a good independent predictor of GC prognosis (p < 0.05). Patients with high METTL5 expression had better prognosis. The nomogram constructed based on METTL5 expression could predict the prognosis of GC patients well. GSEA analysis showed that genes of METTL5 low expression group were enriched in some oncogenic signaling pathways such as ERBB, MAPK, JAK-STAT, Wnt, and mTOR, as well as some immune pathways, including Fc-gamma R mediated phagocytosis, Fc-epsilon Ri, chemokine, T cell receptor and B cell receptor signaling pathway. While the high expression group of METTL5 was mainly related to oxidative phosphorylation, nucleotide excision repair and mismatch repair.ConclusionsMETTL5 protein was decreased in GCTs compared with AIMTs and ANTs, and it may be a potential prognostic biomarker in GC.
Highlights
Ribosomal RNA N6-methyltransferase METTL5 was reported to catalyze m 6A in 18S rRNA
Expression features of METTL5 protein in different gastric lessions In our study, we found that the level of METTL5 protein expression in adjacent normal tissues (ANTs) was significantly higher than that in gastric cancer tissues (GCTs) (p < 0.0001) (Fig. 2a)
On the same immunohistochemical sheet, almost no staining was observed in GCTs, while strong staining was observed in ANTs (Fig. 3a–d) (Table 1)
Summary
Ribosomal RNA N6-methyltransferase METTL5 was reported to catalyze m 6A in 18S rRNA. We aimed to investigate the expression and prognostic features of METTL5 in gastric cancer (GC). The development and progression of GC is a complicated multistep process, including a plenty of genetic and epigenetic changes [2]. Wang et al Cancer Cell Int (2021) 21:569 development and progression, and the identification of risk and prognostic biomarkers, are important to improve early detection and effective treatment of GC. Ribosomal RNA (rRNA) is one of the major ribonucleic acids in living cells and is essential for the production of functional ribosomes, which control protein synthesis and cell function through the translation of the genetic code [3]. Transcription and processing of RNA are very important for cancer cells that need a large number of protein translation to maintain cell growth [3]. RNA enzymes play a crucial part in the processing and maturation of rRNA [4]
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