Overexpression of MTHFD1 in hepatocellular carcinoma predicts poorer survival and recurrence

Future Oncol. 2019 May;15(15):1771-1780. doi: 10.2217/fon-2018-0606. Epub 2019 Apr 18.

Abstract

Aim: MTHFD1 was the enzyme providing one-carbon derivatives of tetrahydrofolate. We sought to investigate the impact of MTHFD1 on hepatocellular carcinoma (HCC). Methods: Bioinformatic analysis, western blot and immunohistochemistry were conducted to detect MTHFD1 expression in HCC. The relationships between MTHFD1 and prognosis of 172 HCCs were analyzed by Kaplan-Meier method and Cox proportional hazards model. Results: High MTHFD1 expression in HCC represented poor prognosis (overall survival p = 0.025; time to recurrence p = 0.044). Combining MTHFD1 with serum AFP, survival analysis demonstrated the prognosis of the MTHFD1 low expression and AFP ≤20 ng/ml group was better than that of the MTHFD1 high expression or AFP >20 ng/ml group and the MTHFD1 high expression and AFP >20 ng/ml group (overall survival p < 0.0001; time to recurrence p < 0.0001). Conclusion: High MTHFD1 expression in HCC indicated poorer prognosis. Combining MTHFD1 with serum AFP improved the accuracy of prognostic prediction.

Keywords: biomarker; hepatocellular carcinoma; immunohistochemistry; prognosis.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality*
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality*
  • Liver Neoplasms / pathology
  • Male
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / genetics*
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / metabolism
  • Middle Aged
  • Minor Histocompatibility Antigens / genetics*
  • Minor Histocompatibility Antigens / metabolism
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Prognosis
  • ROC Curve
  • Reproducibility of Results
  • Risk Factors
  • Tumor Burden
  • alpha-Fetoproteins / metabolism

Substances

  • Biomarkers, Tumor
  • Minor Histocompatibility Antigens
  • alpha-Fetoproteins
  • MTHFD1 protein, human
  • Methylenetetrahydrofolate Dehydrogenase (NADP)