The pattern of expression and prognostic value of key regulators for m7G RNA methylation in hepatocellular carcinoma

Abstract

N7-methylguanosine (m7G) modification on internal RNA positions plays a vital role in several biological processes. Recent research shows m7G modification is associated with multiple cancers. However, in hepatocellular carcinoma (HCC), its implications remain to be determined. In this place, we need to interrogate the mRNA patterns for 29 key regulators of m7G RNA modification and assess their prognostic value in HCC. Initial, the details from The Cancer Genome Atlas (TCGA) database concerning transcribed gene data and clinical information of HCC patients were inspected systematically. Second, according to the mRNA profiles of 29 m7G RNA methylation regulators, two clusters (named 1 and 2, respectively) were identified by consensus clustering. Furthermore, robust risk signature for seven m7G RNA modification regulators was constructed. Last, we used the Gene Expression Omnibus (GEO) dataset to validate the prognostic associations of the seven-gene risk signature. We figured out that 24/29 key regulators of m7G RNA modification varied remarkably in their grades of expression between the HCC and the adjacent tumor control tissues. Cluster one compared with cluster two had a substandard prognosis and was also positively correlated with T classification (T), pathological stage, and vital status (fustat) significantly. Consensus clustering results suggested the expression pattern of m7G RNA modification regulators was correlated with the malignancy of HCC strongly. In addition, cluster one was extensively enriched in metabolic-related pathways. Seven optimal genes (METTL1, WDR4, NSUN2, EIF4E, EIF4E2, NCBP1, and NCBP2) were selected to establish the risk model for HCC. Indicating by further analyses and validation, the prognostic model has fine anticipating command and this probability signature might be a self supporting presage factor for HCC. Finally, a new prognostic nomogram based on age, gender, pathological stage, histological grade, and prospects were established to forecast the prognosis of HCC patients accurately. In essence, we detected association of HCC severity and expression levels of m7G RNA modification regulators, and developed a risk score model for predicting prognosis of HCC patients’ progression.

Constructing and validating of m7G-related genes prognostic signature for hepatocellular carcinoma and immune infiltration: potential biomarkers for predicting the overall survival

“…m7G regulates cellular proliferation and maturation, both of which have been associated to cancer development. A recent study discovered that changes in the process of programmed tumor cell death may enhance the focused therapeutic effect of LIHC ( 31 ). As a result, early detection and diagnosis of the condition are critical.…”

“…A recent study discovered that changes in the process of programmed tumor cell death may enhance the focused therapeutic effect of LIHC (31). As a result, early detection and diagnosis of the condition are critical.…”

M7G-related molecular subtypes can predict the prognosis and correlate with immunotherapy and chemotherapy responses in bladder cancer patients

“…In glioblastoma, a study constructed a signature by four m7G-related genes (TMOD2, CACNG2, PLOD3, and TMSB10) and could predict the prognosis of glioblastoma patients [ 14 ]. Li et al [ 15 ] identified m7G-related clusters that could predict the prognosis of hepatocellular carcinoma patients. Furthermore, in the field of urological tumors, three studies demonstrated the prognostic value of m7G-related mRNAs, lncRNAs and miRNAs in clear cell renal cell carcinoma [ 16 – 18 ].…”

METTL1 mediated tRNA m 7 G modification promotes leukaemogenesis of AML via tRNA regulated translational control

“…The m 7 G modi cation is catalyzed by a highly conserved methyltransferase complex -methyltransferase like 1 (METTL1) and WD repeat domain 4 (WDR4) in mammalian [26,27]. Recent studies have found that METTL1/WDR4 mediated RNA m 7 G modi cation plays important biological roles in human malignancies, such as cancers in the liver, colorectal, esophageal, bladder and lung [22,28,29]. Despite its functional importance in the aforementioned multiple solid tumors, the precise role and regulatory mechanism of METTL1/WDR4 in AML leukeamogenesis remains unclear.…”