Research Paper Volume 15, Issue 21 pp 12192—12208

N7-methylguanosine-related miRNAs predict hepatocellular carcinoma prognosis and immune therapy

Liping Ma1, *, , Qingwei Ma1, *, , Qiaomei Deng1, , Jilu Zhou1, , Yingpei Zhou1, , Qianqian Wei1, , Zhihu Huang1, , Xiaoxia Lao1, , Ping Du2, ,

  • 1 Department of Clinical Laboratory, Minzu Hospital of Guangxi Zhuang Autonomous Region, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, Guangxi, China
  • 2 Department of Gynecology, Minzu Hospital of Guangxi Zhuang Autonomous Region, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, Guangxi, China
* Equal contribution and share first authorship

Received: June 30, 2023       Accepted: October 3, 2023       Published: November 3, 2023
How to Cite

Copyright: © 2023 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


N7-methylguanosine (m7G) modification has been notably linked with the development of many tumors. However, no investigations have been conducted on whether m7G-related miRNA (m7G-miRNA) is a prognostic index of hepatocellular carcinoma (HCC). Therefore, this investigation aimed to establish a predictive m7G-miRNA signature for efficient HCC prognosis and elucidate the associated immune cell infiltration (ICI) and functions in the tumor microenvironment. RNA sequencing and clinical data on 375 HCC and 50 healthy tissue samples were acquired from The Cancer Genome Atlas database. The m7G-miRNA regulators methyltransferase-like 1 and WD repeat domain 4 were acquired from the TargetScan database. Univariate Cox regression analysis was conducted on the 63 differentially expressed m7G-miRNAs identified. A prognostic signature that consisted of seven miRNAs was identified. According to their risk scores, individuals with HCC were divided into high-risk (HR) and low-risk (LR) cohorts. A Kaplan-Meier test revealed that survival in the HR HCC patients was poorer than in the LR cohort (p < 0.001). The area under the receiver operating characteristic curves of 1-, 3-, and 5-year overall survival were 0.706, 0.695, and 0.715, respectively. A nomogram of sex, risk score, age, and stage indicated the HCC patients’ overall survival. Furthermore, it was indicated that the HR and LR patients had different degrees of ICI and immune function. A pathway enrichment analysis revealed the association of several immunity-linked pathways with the risk model. In conclusion, the signature established has great prognostic value and could be used as a new immunotherapy target for individuals with HCC.


HCC: Hepatocellular carcinoma; METTL1: Methyltransferase-like 1; WDR4: WD repeat domain 4; m7G: N7-methylguanosine; miRNAs: MicroRNAs; mRNA: messenger RNA; TCGA: The Cancer Genome Atlas; DEmiRNAs: Differentially expressed miRNAs; ROC: receiver operating characteristic; HR: high-risk; LR: low-risk; AUC: area under the curve; PCA: principal component analysis; OS: overall survival; ESTIMATE: MAlignant Tumour tissues using Expression data; DEGs: Differentially expressed genes; coDEGs: co-differentially expressed genes; HIS: high immune score; LIS: low immune score; FC: fold change FDR;; BP: biological processes; CC: cellular component; MF: molecular function; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; ICI: immune cell infiltration; ssGSEA: Single sample gene set enrichment analysis; vIFITM1: interferon-induced transmembrane protein 1; MTHFD2: methylenetetrahydrofolate dehydrogenase 2; M2: alternatively activated macrophages.