Relationship between MTHFR 677C > T polymorphism and serum PIVKA-II levels in hepatocellular carcinoma.

[BACKGROUND] Hepatocellular carcinoma (HCC) is a major public health problem with increasing incidence and mortality worldwide. The methylenetetrahydrofolate reductase (MTHFR) 677 C > T polymorphism is associated with the development and progression of various tumours, while protein induced by vitamin K absence II (PIVKA-II) is an important tumour marker for the diagnosis of HCC. This study aims to investigate the relationship between the MTHFR 677 C > T polymorphism and serum PIVKA-II levels in HCC patients, providing new insights for early diagnosis, risk assessment, and prognosis evaluation of HCC.

[METHODS] This study included 120 HCC patients and 100 healthy controls. MTHFR 677 C > T genotyping was performed using fluorescent quantitative PCR, and serum PIVKA-II levels were measured. Bioinformatics analysis was used to explore the expression of the MTHFR gene in HCC and its relationship with prognosis.

[RESULTS] MTHFR 677 C > T TT carriers had an increased risk of HCC (OR = 2.393; 95% CI 1.055-5.429;  = 0.037); the risk of HCC for T gene carriers was 58.3% higher than that for C gene carriers in the allele model (OR = 1.583; 95% CI 1.059-2.364;  = 0.025). The difference in serum PIVKA-II concentration was statistically significant between the controls, stage I-II patients, and stage III-IV patients ( < 0.05), and the difference in serum PIVKA-II concentration was statistically significant between patients with the TT genotype and patients with the CC and CT genotypes (all values less than 0.05). UALCAN database analysis showed that MTHFR gene expression levels were increased in patients with HCC, and the high expression of the MTHFR gene was negatively correlated with patient survival rates.

[CONCLUSIONS] There is an association between the MTHFR 677 C > T TT genotype and serum PIVKA-II levels in HCC. This could help identify high-risk individuals and assess disease severity, providing a potential genetic biomarker for the diagnosis of HCC.