Relation between GSTP1 polymorphism and oxidative stress in patients with hepatocellular carcinoma.

BACKGROUND: Glutathione can reduce the oxidative stress by converting the unstable to stable molecules and its status in hepatocellular carcinoma (HCC) is correlated with tumor growth and metastasis. Glutathione S-transferase Pi (GSTP1) is reported to detoxify the xenobiotic substrates by catalyzing their conjugation to reduced glutathione (GSH) and its over-expression was demonstrated in the early stages of HCC, while loss of GSTP1 has been suggested to increase the risk of deoxyribonucleic acid (DNA) damage and mutation. The aim of this study is to assess the relationship of GSTP1 polymorphism Ile105Val (rs1695 A > G) with HCC risk, and to investigate the oxidative stress status of HCC patients by measuring the antioxidant glutathione (GSH) levels. This study was conducted on 99 newly diagnosed HCC patients and 80 apparently healthy individuals as a normal control group. All participants were subjected to the measurement of plasma GSH levels according to Ellman's method, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the detection of GSTP1 polymorphismIle105Val (rs1695 A > G). RESULTS: The occurrence of either the mutant homozygous or the mutant heterozygous genotype of GSTP1 was significantly higher in HCC patients, while the occurrence of the wild genotype was significantly higher among the normal control subjects. Mutant GSTP1 genotype, older age, male gender, and high serum alanine aminotransferase (ALT) were associated with increased risk of development of HCC. The best sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), and overall diagnostic performance for plasma GSH at a cutoff level of 2003.5 µM/mg were 57.6%, 52.5%, 60%, and 40%. The area under the curve for GSH was 0.562. CONCLUSION: Mutant GSTP1 genotype was an independent prognostic factor for increased HCC risk which can be used in a risk assessment model for HCC. Plasma GSH presents insufficient sensitivity and specificity for HCC.

Clinical utility of simple non-invasive liver fibrosis indices for predicting hepatocellular carcinoma (HCC) among Egyptian patients.

AIM: Serological indices for liver fibrosis have been widely used to estimate liver fibrosis, but as far as we know they have not been tested to predict hepatocellular carcinoma (HCC). Our aim is to study the clinical usefulness of some simple non-invasive fibrosis indices in the prediction of HCC among Egyptian patients. METHODS: Ninety patients with HCC who were presented to the National Cancer Institute, Cairo University, were included in this study, together with 30 patients with cirrhosis as a benign control group and 30 apparently healthy volunteers as a normal control group. FIB4 Score, Aspartate Aminotransferase (AST) to Platelet (PLT) Ratio Index (APRI) Score, AST/PLT ratio, Age/PLT Index and AST/alanine aminotransferase indices were calculated for all patients and controls and were tested for their clinical use to predict HCC. RESULTS: Double combination between alpha-fetoprotein and FIB4 Score when either one was abnormal showed the highest diagnostic performance between the HCC group and the cirrhosis and control groups with sensitivity and specificity of (93% and 96%), respectively, whereas the APRI Score was the best to differentiate between the cirrhosis and control groups with sensitivity and specificity of 100% each. CONCLUSIONS: Using some simple non-costly indices can accurately predict HCC and differentiate it from cirrhosis and normal control cases among Egyptian patients, it can also differentiate cirrhosis from normal controls, so can be used as diagnostic and screening tools for both HCC and liver cirrhosis among the Egyptian population.

Can Glypican3 be diagnostic for early hepatocellular carcinoma among Egyptian patients?

BACKGROUND: Because of the high prevalence of hepatocellular carcinoma (HCC) in Egypt, new markers with better diagnostic performance than alpha-feto protein (AFP) are needed to help in early diagnosis. The aim of this work was to compare the clinical utility of both serum and mRNA glypican3 (GPC3) as probable diagnostic markers for HCC among Egyptian patients. MATERIALS AND METHODS: A total of 60 subjects, including 40 with HCC, 10 with cirrhosis and 10 normal controls were analyzed for serum GPC3 (sGPC3) by ELISA. GPC-3 mRNA from circulating peripheral blood mononuclear cells was amplified by RT-PCR. Both markers were compared to some prognostic factors of HCC, and sensitivity of both techniques was compared. RESULTS: Serum glypican-3 and AFP were significantly higher in the HCC group compared to cirrhotic and normal controls (p<0.001). Sensitivity and specificity were (95% each) for sGlypican-3, (82.5% and 85%) for AFP, and (100% and 90%) for Glypican3 mRNA , and (80% and 95%) for double combination between sGPC3 and AFP respectively. CONCLUSION: Both serum GPC-3 and GPC-3mRNA are promising diagnostic markers for early detection of HCC in Egyptian patients. RT- PCR proved to be more sensitive (100%) than ELISA (95%) in detecting glypican3.