Folate and vitamin B-6 status are not associated with homocysteine, oxidative stress and antioxidant capacities in patients with hepatocellular carcinoma

Sb, Cheng; Ht, Liu; Pt, Lin; Lai, Carla; Huang, YC

doi:10.1038/ejcn.2015.222

Cited by 4 publications

(3 citation statements)

References 9 publications

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“…24,25 Studies have shown an inverse association between blood folate levels and HCC risk. 26–30 Therefore, folate status also may be associated with HCC prognosis. More advanced stage HCC patients have lower folate levels than those with earlier stage disease, but no study examined the role of circulating folate in survival of HCC patients.…”

Section: Discussionmentioning

confidence: 99%

Global Level of Plasma DNA Methylation is Associated with Overall Survival in Patients with Hepatocellular Carcinoma

et al. 2017

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Background The impact of folate deficiency on global DNA methylation is uncertain. It also is unclear whether global DNA methylation is associated with outcome in HCC. LINE-1 methylation levels, as a surrogate marker of global methylation, may be influenced by folate deficiency. However, the interaction between LINE-1 methylation and folate level on overall survival (OS) in hepatocellular carcinoma (HCC) patients is unknown. We evaluated whether LINE-1 hypomethylation and folate deficiency are associated with HCC prognosis. Methods We prospectively recruited 172 HCC patients between 2008 and 2012. LINE-1 methylation levels in plasma and white blood cells (WBC) were measured by pyrosequencing, and plasma folate levels by a radioprotein-binding assay. Results Patients with plasma LINE-1 methylation <70.0% (hypomethylation) had significantly worse OS compared with those with ≥70.0% methylation (hypermethylation) [hazard ratio (HR) = 1.77; 95% confidence interval (CI) 1.12–2.79; P = 0.015]. HCC patients with lower plasma folate levels also had worse survival (<27.7 vs. ≥27.7 nmol/L; HR = 1.96; 95% CI, 1.24–3.09; P = 0.004). Furthermore, survival was poor in patients in whom both plasma LINE-1 methylation and folate levels were low compared with those patients in whom both levels were high (HR = 3.36; 95%CI, 1.77–6.40; P <0.001). This interaction neared statistical significance (P = 0.057). No significant association was found between WBC LINE-1 methylation levels and survival. Conclusions These findings suggest that both lower plasma levels of LINE-1 methylation and folate are associated with worse survival in HCC patients.

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Section: Discussionmentioning

confidence: 99%

Global Level of Plasma DNA Methylation is Associated with Overall Survival in Patients with Hepatocellular Carcinoma

et al. 2017

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“…Consistently, Lin CC et al [ 19 ] showed that plasma level of folate in HCC patients was significantly lower compared to healthy controls, in spite of very small sample size in their study (40 cases and 20 controls). Recently, Cheng et al [ 20 ] showed that HCC patients at preresection had lower serum folate than that of control groups. Chang et al [ 21 ] also observed an inverse association between plasma folate levels and liver cancer.…”

Section: Discussionmentioning

confidence: 99%

Plasma Folate and Vitamin B12 Levels in Patients with Hepatocellular Carcinoma

Cui

Quan

Piao

et al. 2016

IJMS

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Folate and vitamin B12 involved in the one-carbon metabolism may play a key role in carcinogenesis and progression of hepatocellular carcinoma (HCC) through influencing DNA integrity. The purpose of this study is to evaluate the association of plasma folate and vitamin B12 levels with HCC in a case-control study on 312 HCC patients and 325 cancer-free controls. Plasma concentrations of folate and vitamin B12 in all the subjects were measured by electrochemiluminescence immunoassay. Meanwhile, the information of HCC patients’ clinical characteristics including tumor-node-metastasis (TNM) stage, tumor size and tumor markers were collected. The patients of HCC had significantly lower folate levels than those of controls; there was no significant difference in the mean of plasma vitamin B12 levels. We also observed an inverse association between the levels of plasma folate and HCC: the adjusted odds ratios (OR) (95% confidence intervals (CI)) of HCC from the highest to lowest quartile of folate were 0.30 (0.15–0.60), 0.33 (0.17–0.65), and 0.19 (0.09–0.38). Compared to the subjects in the lowest quartile of plasma vitamin B12, only the subjects in the highest quartile of vitamin B12 exhibited a significant positive relationship with HCC, the adjusted OR was 2.01 (95% CI, 1.02–3.98). HCC patients with Stage III and IV or bigger tumor size had lower folate and higher vitamin B12 levels. There was no significant difference in the mean plasma folate levels of the HCC cases in tumor markers status (AFP, CEA and CA19-9 levels), whereas patients with higher CEA or CA19-9 levels retained significantly more plasma vitamin B12 than those with normal-CEA or CA19-9 level. In conclusion, plasma folate and vitamin B12 levels could be associated with HCC, and might be used as predictors of clinical characteristics of HCC patients. However, further prospective studies are essential to confirm the observed results.

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“…Recently, scholars 38 have found that VB6 is related to the metabolism of H 2 S, H 2 S 2 , cystine, cysteine, homocysteine, cystine sulfide, and methionine in the metabolic reprogramming of liver cancer. 39 Many clinical trials [40][41][42] have observed an anti-hepatocellular carcinoma effect by directly…”

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confidence: 99%

Vitamin B6 Metabolic Pathway is Involved in the Pathogenesis of Liver Diseases via Multi-Omics Analysis

Mei¹,

Liu²,

Tang³

et al. 2022

JHC

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Purpose To clarify the underlying regulatory mechanisms of progression from liver cirrhosis to hepatocellular carcinoma (HCC), we analyzed the microbiomics, metabolomics, and proteomics in plasma and tissues from patients with HCC or decompensated liver cirrhosis (DC). Patients and Methods Tissues and plasma from 44 HCC patients and 28 patients with DC were collected for metabolomic analysis. 16S rRNA sequencing was performed in nine HCC tissues (HCCT), four distal noncancerous tissues (HCCN), and 11 DC tissues (DCT). Five HCC tissues had liver cirrhosis (HCCT-LC). Five hepatocellular carcinoma tissues without liver cirrhosis (HCCT-NLC) and five DCT were selected for proteomic sequencing. After combining proteomic and metabolomic analysis, we constructed a mouse model of chronic liver injury using carbon tetrachloride (CCl4) and treated them with vitamin B6 (VB6). Results 16s rRNA sequence results showed that HCC tissues had higher alpha diversity. The highest LDA scores were detected for Elizabethkingia in HCCT, Subsaxibacter in DCT, and Stenotrophomon in HCCN. Metabolomics results demonstrated some metabolites, including capric acid, L-threonate, choline, alpha-D-Glucose, D-ribose, betaine, 2E-eicosenoic acid, linoleic acid, L-palmitoylcarnitine, taurodeoxycholic acid, L-pyroglutamic acid, androsterone sulfate, and phthalic acid mono-2-ethylhexyl ester (MEHP), had better diagnostic efficacy than AFP (AUC: 0.852; 95% CI: 0.749, 0.954). In a combined analysis of metabolomics and proteomics, we found that HCCT-LC had more obvious disorders of VB6 metabolism and pentose and glucuronate interconversions than DCT, and kynurenine metabolism disorder was more significant in HCCT-LC than in HCCT-NLC. In the CCl4-induced chronic liver injury model, after VB6 supplementation, inflammatory cell infiltration, hepatocyte edema, and degeneration were significantly improved. Conclusion We found significant differences in the flora distribution between HCCT and DC; MEHP was a new diagnostic biomarker of HCC, and VB6 ameliorated the inflammatory cell infiltration, hepatocyte edema, and degeneration in chronic liver injury.

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Folate and vitamin B-6 status are not associated with homocysteine, oxidative stress and antioxidant capacities in patients with hepatocellular carcinoma

Cited by 4 publications

References 9 publications

Global Level of Plasma DNA Methylation is Associated with Overall Survival in Patients with Hepatocellular Carcinoma

Global Level of Plasma DNA Methylation is Associated with Overall Survival in Patients with Hepatocellular Carcinoma

Plasma Folate and Vitamin B12 Levels in Patients with Hepatocellular Carcinoma

Vitamin B6 Metabolic Pathway is Involved in the Pathogenesis of Liver Diseases via Multi-Omics Analysis

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