Abstract: Objective To explore the expression level, prognostic value and relationship with immune microenvironment of folate metabolic pathway key genes (FMGs) in hepatocellular carcinoma (HCC) through bioinformatics analysis.Methods The expression levels of FMGs (MTR, MTHFR, MTHFD1, MTHFD2, SHMT1 and SHMT2) in HCC were analyzed by Oncomine and GEPIA. The relationship between FMGs and clinical prognosis was assessed by Kaplan-Meier survival curve. The genetic changes of FMGs were observed by cBioPortal. The interaction network of FMGs was constructed by STRING and GeneMANIA. The relationship of FMGs and immune infiltratimh cells was analyzed by TIMER database.Results Oncomine and GEPIA online analysis showed that the relative mRNA expression levels of MTR and MTHFD2 in HCC were 2 and 1.6 folder higher than those in normal liver tissues (P<0.05). cBioPortal analysis revealed that genetic changes of FMGs in HCC included gene amplification, deletion mutation and missense mutation. Kaplan-Meier survival analysis demonstrated that the high mRNA expression level of MTHFR was significantly associated with poor prognosis [hazard ratio (HR)=1.49, P=0.04], while the high expression levels of MTHFD1 and SHMT1 were significantly associated with favorable prognosis (HR=0.63, P=0.008 9 and HR=0.52, P=0.00031). TIMER analysis suggestted that MTHFR and MTHFD2 were postively correlated with the infiltration of diverse immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells.Conclusion FMGs is significantly correlated with the clinical prognosis of HCC patients and infiltration of immune cells, it is also a potential therapeutic target and a prognostic biomarker of HCC.

Key words: Hepatocellular carcinoma, Folate metabolic pathway, Prognosis, Immune, Bioinformatics