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Abstract <p>Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths globally. In HCC, metabolic reprogramming leads to increased methionine synthesis, from homocysteine, which promotes tumor cell growth. Hyperhomocysteinemia often cause folate depletion. The present preliminary study was conducted to evaluate the diagnostic significance of MTR gene, homocysteine and 5-MTHF levels in HCC patients. A total of 40 participants were recruited in this study. HCC patients had higher homocysteine and reduced 5-MTHF levels as determined by enzyme cycling assay. mRNA expression of MTR gene was 5.6-fold higher in HCC patients relative to the control. A positive but moderate correlation (<i>r</i> = 0.61) was found between MTR gene and homocysteine levels while negative correlation (<i>r</i> = –0.67) was noted between MTR gene and 5-MTHF levels. Docking studies identified ALA442.A, GLY465.A and CYS463.A as potential amino acid residues of MTR protein interacting with homocysteine. Similarly, GLY38.A and ASP68.A of MTR protein were found to be potentially involved in hydrogen bond formation with 5-MTHF. The association of MTR gene with age and sex was not statistically significant. The study also reported that in HCC patients, homocysteine level, MTR gene expression, and prothrombin time were all upregulated while 5‑MTHF and albumin levels were reduced. Overall, the study provided complex interplay between the metabolites of one carbon metabolism (OCM) and their diagnostic and therapeutic potential. The results suggested that serum homocysteine, 5-MTHF levels, and MTR gene expression may serve as potential diagnostic biomarkers and may predict patient outcome in HCC.</p>

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Molecular Triad of MTR, Homocysteine, and 5-MTHF in HCC: Towards Novel Diagnostic Markers

  • 期刊论文

  • 发表日期：

    2026年3月1日

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  • A. Nudrat,
  • S. E. Zahra,
  • T. Wali,
  • N. Rehman,
  • F. Naz,
  • S. Zia

摘要

Abstract

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths globally. In HCC, metabolic reprogramming leads to increased methionine synthesis, from homocysteine, which promotes tumor cell growth. Hyperhomocysteinemia often cause folate depletion. The present preliminary study was conducted to evaluate the diagnostic significance of MTR gene, homocysteine and 5-MTHF levels in HCC patients. A total of 40 participants were recruited in this study. HCC patients had higher homocysteine and reduced 5-MTHF levels as determined by enzyme cycling assay. mRNA expression of MTR gene was 5.6-fold higher in HCC patients relative to the control. A positive but moderate correlation (r = 0.61) was found between MTR gene and homocysteine levels while negative correlation (r = –0.67) was noted between MTR gene and 5-MTHF levels. Docking studies identified ALA442.A, GLY465.A and CYS463.A as potential amino acid residues of MTR protein interacting with homocysteine. Similarly, GLY38.A and ASP68.A of MTR protein were found to be potentially involved in hydrogen bond formation with 5-MTHF. The association of MTR gene with age and sex was not statistically significant. The study also reported that in HCC patients, homocysteine level, MTR gene expression, and prothrombin time were all upregulated while 5‑MTHF and albumin levels were reduced. Overall, the study provided complex interplay between the metabolites of one carbon metabolism (OCM) and their diagnostic and therapeutic potential. The results suggested that serum homocysteine, 5-MTHF levels, and MTR gene expression may serve as potential diagnostic biomarkers and may predict patient outcome in HCC.