Objective Epigenetic reprogramming plays a key role in the progression of cholangiocarcinoma(CCA).m7G modi-fication is one of the most common base modifications in post transcriptional regulation,which plays the huge role in many tu-mors related biological activities such as proliferation,invasion and metastasis by regulating expression of tumor related genes,and to explore the modification patterns related to construction of m7G methylation regulatory factors and their evaluation of clini-cal prognosis and therapeutic efficacy in CCA.Methods The expression level of 27 m7G regulatory factors[Argonaute2(AGO2),fragile X mental retardation 1 protein(FMR1),cytoplasmic FMR1 interacting protein 1(CYFIP1),decapping mRNA 2(DCP2),scavenger decapping enzyme(DCPS),eukaryotic initiation factor(EIF3),EIF3 subunit D(EIF3D),EIF4A1,EIF4E,EIF4E family member 1B(EIF4E1B),EIF4E family member 2(EIF4E2),EIF4E family member 3(EIF4E3),EIF4E gama 3(EIF4G3),gem nuclear organelle associated protein 5(GEMIN5),interferon-induced protein with tetratricopeptide repeats 5(IFIT5),La ribonu-cleoprotein 1(LARP1),Sm-like-1(LSM1),methyltransferase 1(METTL1),nuclear cap-binding protein(NCBP)1,NCBP2,NCBP2-like(NCBP2L),NOP2/Sun RNA methyltransferase 2(NSUN2),nudix hydroxylase(NUDT)10,NUDT3,NUDT4,snurportin 1(SNUPN),WD repeat domain 4(WDR4)]were analyzed based on Cancer Genome Map(TCGA)and Gene Expression Comprehen-sive Database(GEO),and survival analysis were conduct using clinical data from CCA patients.The consensus clustering analysis was performed on all patient data and differential expression genes(DEG)related to prognosis were screened.The consensus clustering analysis was performed to detect the effects of m7G methylation regulators and their DEG,the m7G methylation scoring system was further established to evaluate the correlation between m7G methylation score and prognosis of CCA patients.Results About 48％(12/25)m7G methylation regulatory factor DNA copy number increased,of which AGO2 copy number increased the most;about 56％(14/25)m7G methylation regulators DNA copy number decreased,of which EIF4G3 decreased the most and closely related to patient prognosis.In addition to IFIT5,there was complex and close interaction in remaining regulatory factors.Among the 17 m7G methylation regulatory genes related to prognosis of CCA patients,the high expressions of LARP1,NUDT3,SNUPN,NCBP2,EIF4E1B,NUDT11,NSUN2,EIF4A1,GEMIN5 and CYFIP1 were positively correlated with patient prognosis,and the high expressions of EIF4E3,WDR4,EIF4E2,NUDT4,NCBP1,EIF4E and DCP2 were related to poor prognosis of patients(P＜0.05).The intersection DEG between m7G methylation types was taken,and DEG was mainly enriched in vascular endothe-lial cell proliferation and neovascularization.The prognosis-related genes were screened and two subgroups of m7G methylation gene characteristics with different prognosis were obtained.The difference between 2 groups of m7G methylation scores was statis-tically significant,and patient prognosis with low m7G methylation score was relatively good.Conclusion It is demonstrated that the abnormality of m7G modification is closely related to the occurrence and development of CCA,which plays an important role in the formation of tumor regulatory network.Assessing the m7G modification pattern in tumors will help guide the development of more effective treatment strategies.
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