Identification of three m6A‐related mRNAs signature and risk score for the prognostication of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is extremely harmful to human health. In recent years, N6‐methyladenosine (m6A) RNA methylation in eukaryotic mRNA has been increasingly implicated in cancer pathogenesis and prognosis. In this study, we downloaded the expression profile and clinical information of 307 patients from The Cancer Genome Atlas database and 64 patients from the Gene Expression Omnibus (GEO) database, and univariate Cox analysis revealed that METTL14 was a prognostic m6A RNA methylation regulator. For further study on the related genes of METTL14, weighted gene co‐expression network analysis was used to find the relationship between METTL14 and gene expression, and univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) methods were used to identify hub genes that may be associated with HCC prognosis. The results indicated that cysteine sulfinic acid decarboxylase, glutamic‐oxaloacetic transaminase 2, and suppressor of cytokine signaling 2 were key genes affecting the prognosis of HCC patients, and m6A methylation of these mRNAs may be regulated by METTL14. Finally, a nomogram was constructed based on the hub gene expression levels, and its prediction accuracy and discriminative ability were measured by the C‐index and a calibration curve. In conclusion, METTL14, an m6A RNA methylation regulator, may participate in the malignant progression of HCC by adjusting the m6A of cysteine sulfinic acid decarboxylase, glutamic‐oxaloacetic transaminase 2, and suppressor of cytokine signaling 2, and these genes are useful for prognostic stratification and treatment strategy development.

Expression of m6A Regulators Correlated With Immune Microenvironment Predicts Therapeutic Efficacy and Prognosis in Gliomas

“…Besides, the "erasers" comprise fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5) (Jia et al, 2011;Zheng et al, 2013). Various studies have revealed that m6A regulators can be used as novel prognostic biomarkers in different types of cancer (Chen et al, 2019;Fang and Chen, 2020;Huang et al, 2020a;Li Z. et al, 2020;Lu et al, 2020). METTL3 was shown to promote the proliferation and migration of hepatocellular carcinoma via the YTHDF2-dependent pathway and its knockdown could inhibit tumor progression (Chen et al, 2018).…”

Identification and validation of m6A RNA methylation regulators with clinical prognostic value in Papillary thyroid cancer

“…Numerous studies showed that m 6 A RNA methylation played a role in the occurrence and progression of multiple malignant tumors, including hepatocellular carcinoma, colorectal carcinoma, breast cancer, glioblastoma and clear cell renal cell carcinoma [12][13][14][15]. Yongsheng li et al have concluded the characteristics of m 6 A RNA methylation across 33 types of cancer and predicted that the mechanism of m 6 A RNA modification might be related with the activation or depression of some oncogenic pathways such as PI3K-AKT-mTOR signaling, G2M checkpoint, KRAS and P53 pathways [16].…”

Gene Risk Signature of m6A Regulators, KIAA1429, YTHDF1, YTHDF2, METTL3 and Its Relationship with Immune Infiltration in Hepatocellular Carcinoma

“…Increased METTL14 expression inhibited the ability of migration and invasion in vitro tumor cell (41). METTL14 may play a role in the progression of HCC by regulating the m6A levels of CSAD, GOT2, and SOCS2 (42). In this study, we also found that KIAA1429 protein expression was not detected in normal liver tissues and HCC tissues.…”