Identification and validation of N7 -methylguanosine-associated gene NCBP1 as prognostic and immune-associated biomarkers in breast cancer patients

J Cell Mol Med. 2024 Jan;28(2):e18067. doi: 10.1111/jcmm.18067. Epub 2023 Dec 10.

Abstract

We intend to evaluate the importance of N7 -methylguanosine (m7G) for the prognosis of breast cancer (BC). We gained 29 m7G-related genes from the published literature and among them, 16 m7G-related genes were found to have differential expression. Five differentially expressed genes (CYFIP1, EIF4E, EIF4E3, NCBP1 and WDR4) were linked to overall survival. This suggests that m7G-related genes might be prognostic or therapeutic targets for BC patients. We put the five genes to LASSO regression analysis to create a four-gene signature, including EIF4E, EIF4E3, WDR4 and NCBP1, that divides samples into two risky groups. Survival was drastically worsened in a high-risk group (p < 0.001). The signature's predictive capacity was demonstrated using ROC (10-year AUC 0.689; 10-year AUC 0.615; 3-year AUC 0.602). We found that immune status was significantly different between the two risk groups. In particular, NCBP1 also has a poor prognosis, with higher diagnostic value in ROC. NCBP1 also has different immune states according to its high or low expression. Meanwhile, knockdown of NCBP1 suppresses BC malignancy in vitro. Therefore, m7G RNA regulators are crucial participants in BC and four-gene mRNA levels are important predictors of prognosis. NCBP1 plays a critical target of m7G mechanism in BC.

Keywords: N7-methylguanosine; NCBP1; breast cancer; differentially expressed genes; immune.

MeSH terms

  • Biomarkers
  • Breast Neoplasms* / genetics
  • Eukaryotic Initiation Factor-4E
  • Female
  • GTP-Binding Proteins
  • Guanosine* / analogs & derivatives
  • Humans
  • Nuclear Cap-Binding Protein Complex / metabolism
  • Prognosis

Substances

  • 8-methylguanosine
  • Biomarkers
  • Eukaryotic Initiation Factor-4E
  • GTP-Binding Proteins
  • Guanosine
  • Nuclear Cap-Binding Protein Complex
  • WDR4 protein, human