Role of serum glypican-3 in the diagnosis and differentiation of small hepatocellular carcinoma from hepatitis-C virus cirrhosis

Background: Serum alpha-fetoprotein (AFP) has insufficient sensitivity and specificityfor detection of hepatocellular carcinoma (HCC). Recently, glypican-3 (GLP-3) was suggested as a new biomarker for the detection HCC.Objectives: To determine the role of serum GLP-3 levels in the early diagnosis and differentiation of small (3 cm or less in diameter) HCC from liver cirrhosis. Also, to correlate GLP-3 levels to clinico- laboratory data.Methods: The study included sixty patients; 30 of them with hepatitis C virus (HCV) cirrhosis, and 30 patients with proved HCC. In addition, 20 healthy subjects were included as a control group. Clinical and radiological features (abdominal ultrasonography and/or abdominal triphasic computed tomography) were recorded. Liver function tests, complete blood cell count, and serum AFP were measured. Serum GLP-3 values were determined by an ELISA technique.Results: Serum levels of GLP-3 were significantly elevated in patients with HCC compared with HCV cirrhosis group (p< 0.001). Also, these levels were significantly elevated in these two patients’ groups versus controls (p<0.001). Also, serum GLP-3 levels with cut-off value of P240 ug/L, had a higher sensitivity (100%) and same specificity (93.3%), than AFP with cut-off value of P200 ng/ ml, for detection of HCC. Moreover, GLP-3 levels showed a higher sensitivity than AFP (50% vs.41.7%), for detection of small HCC. The combined use of both markers (i.e. when either one of the two markers positive) improved the specificity to 88.9%. Regarding unicentric HCC, GLP-3 at cut-off value of 6580 ug/L had better specificity than AFP at cut-off value of 6765 ng/ml (57.1% vs. 42.9%). The combined use of both markers improved the sensitivity and specificity to 82.6% and 71.4%, respectively. Conclusion: Serum GLP-3 levels are higher in HCC versus HCV cirrhosis, which can differentiate HCC from liver cirrhosis. Also, serum GLP-3 is highly sensitive and specific for detecting HCC. Moreover, GLP-3 is more sensitive than AFP for the detection of small HCC. Furthermore, a combination of both serum markers yielded an improved specificity and both sensitivity and specificity for the diagnosis of small and unicentric HCC, respectively.Keywords: Serum tumor marker Alpha-fetoprotein Early hepatocellular carcinoma Diagnosis

Role of 11β HSD 1, rs12086634, and rs846910 single-nucleotide polymorphisms in metabolic-related skin diseases: a clinical, biochemical, and genetic study

Azza Gaber Antar Farag,1 Eman AE Badr,2 Abdel Monem A Eltorgoman,3 Mohamed FA Assar,4 Eman N Elshafey,1,4 Nermin Reda Tayel,5 Hossam EA Aboutaleb4 1Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufia University, Shibin El Kom, Egypt; 2Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Shibin El Kom, Egypt; 3Department of Organic Chemistry, Faculty of Science, Menoufia University, Shibin El Kom, Egypt; 4Department of Chemistry, Biochemistry Division, Faculty of Science, Menoufia University, Shibin El Kom, Egypt; 5Department of Molecular Diagnostics and Therapeutics, Genetic Engineering Biotechnology Research Institute, Sadat City, Egypt Background: 11β HSD1 generates cortisol from cortisone. 11β HSD1 single-nucleotide polymorphism (SNP) was associated with metabolic syndrome (MeTS). Although the relation of acne vulgaris (AV) and skin tags (STs) with MeTS has been reported, the relationship between 11β HSD 1 SNP and cortisol activity in those patients has not studied till now.Aims: To investigate, two 11β-HSD1 SNPs (rs846910 and rs12086634), serum lipid profile and cortisol levels in patients with AV and STs in an Egyptian population.Patients and methods: This case–control study was performed on 50 patients having STs and 50 complaining of AV and 50 sex- and age-matched controls. We searched for serum lipid profile, cortisol levels, and 11β-HSD1 rs846910 and rs12086634 SNPs using real time-PCR.Results: Compared to controls,11β-HSD1 rs846910 GA genotype carriers had significantly higher risks for developing AV and STs by 3.4- and 4.9-fold, respectively, and its A allele increases these risks by 3.1 and 4.4 times, respectively. Also, 11β-HSD1 rs12086634 TG genotype increases the risk of AV by 3.2-fold, as well as STs by 3.5-fold, and its G allele increases the risk of AV by 3.2-fold and STs by 7-fold. In AV and ST patients, rs846910 GA genotype demonstrated significant associations with elevated body mass index (BMI), and cholesterol, low density lipoprotein (LDL), cortisol, and decreased high density lipoprotein serum levels, respectively. However, rs12086634 GG genotype was significantly associated with increased BMI, cholesterol, and LDL serum levels in patients with AV and STs, in addition to the number of STs and serum cortisol levels in ST patients.Conclusion: 11β-HSD1 rs846910 and rs12086634 gene polymorphisms may contribute to AV and STs pathogenesis, that may be mediated through enhancing the enzymatic activity (increasing cortisol levels). AV and STs are associated with obesity and atherogenic lipid profile. Diagnosis of AV and STs may play a role in early detection of the MeTS. Keywords: skin tags, acne vulgaris, metabolic syndrome, 11 beta hydroxysteroid dehydrogenase, single-nucleotide polymorphis