Abstract
Although it is widely accepted that N6-methyladenosine (m6A) RNA methylation plays critical roles in tumorigenesis and progression, the values of m6A modification are less known in hepatocellular carcinoma. The major purpose of our current studies is to investigate the role of m6A regulators in hepatocellular carcinoma and whether it can affect the prognosis of hepatocellular carcinoma. Here we demonstrate that most of the m6A regulators are highly expressed in hepatocellular carcinoma. Furthermore, we cluster hepatocellular carcinoma into two subgroups (cluster 1/2) by applying consensus clustering to m6A regulators. Compared with the cluster 1 subgroup, the cluster 2 subgroup was significantly associated with a higher pathological grade and survival. Based on these findings, we reveal a risk signature by using three m6A regulators, which are not only an independent prognostic marker but also a predictor of the clinicopathological features in hepatocellular carcinoma. In conclusion, m6A regulators are crucial participants in the malignant progression of hepatocellular carcinoma and are potential targets for prognosis.
Highlights
RNA modification was first discovered in the 1960s and was considered to be another epigenetic form analogous to DNA and histone modification (Jia et al, 2013)
To further confirm the role of all m6A regulators in hepatocellular carcinoma (HCC), we systematically investigated the expression of 13 m6A regulators in 403 HCC samples and 58 adjacent normal tissue samples from the TCGA database
Similar to the results of Li’s report (Li et al, 2020), we found that KIAA1429, methyltransferase like 3 (METTL3), and heterogeneous nuclear ribonucleoprotein C (HNRNPC) are highly expressed in HCC tumor samples
Summary
RNA modification was first discovered in the 1960s and was considered to be another epigenetic form analogous to DNA and histone modification (Jia et al, 2013). METTL3 serves as a tumor suppressor gene in GBM and is considered as an oncogene in CRC or non-small cell lung carcinoma (Li et al, 2019; Wei et al, 2019; Liu et al, 2020). The literature does not have comprehensive m6A regulator expression and prognosis analysis in tumors. We systematically analyze the expression data of 13 m6A modification regulators in HCC from The Cancer. The interaction and the correlation among m6A regulators were analyzed using the R package “corrplot.” The HCC patients were divided into two subgroups based on the expression of m6A regulators using a cluster analysis method with “ConsensusClusterPlus”. The roles of m6A regulators in the prognosis of HCC patients were identified by univariate Cox regression analysis; p < 0.05 was considered as significant. Complete information on the 403 samples included relevant clinical data for univariate and multivariate Cox regression analyses. p < 0.05 was considered as statistically significant
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