ABSTRACT
BACKGROUND/AIMS: Because there is a lack of effective biomarkers, we aimed to discover proteomic candidate markers for hepatocellular carcinoma (HCC) in cirrhotic patients at the highest-risk of HCC, and to validate the markers. METHODS: We collected tumor tissue from 5 cirrhotics with HCC, and from 5 cirrhotics without HCC, who underwent liver resection or transplantation. These tissue samples were analyzed by 2-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and potential markers were validated at the transcriptional and translational levels. We also performed western blot assays using other blood samples from 10 cirrhotics with HCC and 10 without HCC. RESULTS: Among the 66 distinguishable spots on 2-D gel images, we identified 15 proteins overexpressed more than 1.5 fold in terms of volume ratio in the tumors. Ten of the over-expressed proteins were identified by MALDI-TOF MS; of those, only methionine adenosyltransferase 1 (MAT1), a protein specific for liver, and acyl-CoA dehydrogenase were significantly up-regulated in tumors in further immunoblotting analyses (Ps<0.05). There was no between-pair difference in MAT1 mRNA measured by real-time polymerase chain reaction (P=0.96). However, in western blots of serum samples, distinct MAT1 bands were observed in all 10 HCC patients, but in only 2 of the non-HCC patients. CONCLUSIONS: MAT1 is a potential marker for surveillance in cirrhotic patients with and without prior HCC.
Subject(s)
Humans , Acyl-CoA Dehydrogenase , Biomarkers , Blotting, Western , Carcinoma, Hepatocellular , Immunoblotting , Liver , Liver Cirrhosis , Mass Spectrometry , Methionine Adenosyltransferase , Methionine , Proteomics , Real-Time Polymerase Chain Reaction , RNA, Messenger , Two-Dimensional Difference Gel ElectrophoresisABSTRACT
Hypermetioninemia is a group of rare diseases defined by plasma methionine elevation. The causes of hypermethioninemia include genetic and non-genetic factors. Affecting the transmethylation process in the metabolic pathway between methionine and homocysteine is the common inherited methylation disorders. Most patients had completely asymptomatic and only biochemical abnormalities,others with clinical symptoms were also non-specific, such as mental retardation, cognitive impairment, moderate hepatomegaly, dystonia, Marfans syndrome type,osteoporosis,and cardiovascular disease,and etc. A low methionine diet treatment is rec-ommended,the importance of neonatal screening is emphasized and the birth defects can be reduced through pre-natal diagnosis,but the necessity remains controversial. The long-term prognosis of this disorders is unknown,the plasma of methionine should be measured at regular intervals,and the individualized follow-up is very important.
ABSTRACT
Objective To investigate the clinical and molecular genetic characteristics of hypermethioninemia caused by methionine adenosyltransferase deficiency. Methods The clinical data and related gene analysis of hypermethioninemia caused by methionine adenosyltransferase deficiency in 3 children were retrospectively analyzed. The core pedigree analysis was carried out. Results Three children (2 boys and 1 girl) aged from 5 months to 3 years, were from 3 unrelated families. All of them had no family history. One case was found in neonatal screening. One case was onset with pathological jaundice at 1 month old. Another case was found due to tremor and growth retardation at 2 years old. Blood amino acid ester acyl carnitine spectrum analysis showed that all of them had significantly elevated levels of methionine at 134.50-790.67 μmol/L. All children had MAT1A mutation in methionine adenosyltransferase gene. One case was heterozygous mutations with third exon c.274T>C and seventh exon c.895C>T mutation; one case had sixth exon c.757G>A homozygous mutation; and another case had seventh exon c.791G>A homozygous mutation. The core pedigree analysis showed that the mutations were from theirs parents respectively. Conclusions For children with neurologic impairment, methionine metabolic disorders should be considered. Blood amino acids and gene analysis are important methods for confirmation of the diagnosis. Neonatal screening is an effective way to detect this disease.
ABSTRACT
The threat of cancer to human being' s health is definite.In order to find more effective cures,experts has always taking the mechanism of tumorigenesis as a research foucus and hot spot.As everyone knows,the basic biological behaviors of malignant cells have changed a lot,such as cell proliferation,apoptosis,and so on,and the causes are related to the aberrant methylation reaction occurred in these cells.Researchers have found out that DNA methylation in tumor tissues were obviously different from that in normal tissues,with the charateristics of extensive hypomethylation and localized hypermethylation.To identify the effect of abnormal methylation reaction in the evolution and progression of tumor,this article is aiming to overview those previously researches about the abnormal methylation reaction in tumor cell and its effect on cell growth.
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Objective: To study the expression and activity changes of methionine adenosyltransferase (MAT) in human peripheral T lymphocytes. Methods: The expression of MAT mRNA was detected by RT-PCR and the activity of MAT was measured. Results: After stimulated by IL-2, PHA and anti-CD3 antibody, MAT-Ⅱ gene expression increased by (8.9? 2.1), (7.7?1.9) and (8.0?1.8) times, respectively, and the expression peak was at 8, 4 and 8 h,respectively; MAT activity continuously increased in 48 h. S-adenosylmethioinie (SAM) moderately induced IL-2 and IFN secretion by human T cells. SAM(0.1 mg/ml) downregulated the expression and activity of MAT-Ⅱ and the secretion of IL-2 and IFN induced by PHA or anti-CD3 antibody in human T cells. Conclusion:MAT is involved in the activation of T lymphocytes, and high dose of SAM may also inhibit its activation through PHA and anti-CD3 antibody.