Galanin and glypican-4 levels depending on metabolic and cardiovascular risk factors in patients with polycystic ovary syndrome

ABSTRACT Objective: Galanin is a neuropeptide which has effects not only on metabolic syndrome but also on reproduction. Glypican-4 is an adipokine associated with insulin sensitivity by interacting directly with the insulin receptor. This study evaluated serum concentrations of galanin and glypican-4 in relation with the hormonal profile as well as metabolic and cardiovascular risk factors in patients with and without polycystic ovary syndrome (PCOS). Subjects and methods: A total of 44 women with PCOS and 44 age-matched controls were eligible. Hirsutism scores, hormonal profile, metabolic and cardiovascular risk factors as well as galanin and glypican-4 levels were evaluated in each subject. Results: Women with PCOS exhibited lower levels of galanin (20.2 pg/mL versus 26.4 pg/mL, p = 0.002) and higher concentrations of glypican-4 (3.1 ng/mL versus 2.6 ng/mL, p < 0.001) than controls. Both adipokines were correlated positively with body mass index (BMI), insulin, triglyceride and Homeostasis Model Assessment (HOMA) index; glypican-4 also showed positive correlations with fasting blood glucose, free testosterone, modified Ferriman-Gallwey scores (p < 0.05). Multiple Linear Regression analyses showed that PCOS and BMI were the best predictors affecting galanin levels with a decreasing and increasing effect respectively; however BMI was the best predictor affecting glypican-4 levels with an increasing effect (p < 0.001). Conclusion: Galanin levels were lower and glypican-4 levels were higher in women with PCOS than controls. Further studies are needed to determine whether these adipokines could be used as additional markers for insulin sensitivity and lipid profile and whether they might play a role in the pathogenesis of PCOS, in which metabolic cardiovascular risks are increased.

Glypican-3 level assessed by the enzyme-linked immunosorbent assay is inferior to alpha-fetoprotein level for hepatocellular carcinoma diagnosis

BACKGROUND/AIMS: Glypican-3 (GPC3) protein is highly expressed in hepatocellular carcinoma (HCC) tissue. It has been suggested as a diagnostic biomarker, but its inconsistent performance means that it requires further assessment. We therefore investigated the diagnostic value of the plasma GPC3 level compared to the alpha-fetoprotein (AFP) level as a diagnostic biomarker of HCC. METHODS: We enrolled 157 consecutive patients with newly diagnosed HCC and 156 patients with liver cirrhosis (LC) as the control group. GPC3 plasma levels were measured using two commercially available enzyme-linked immunosorbent assays (ELISAs, named as Assay 1 and 2), and AFP levels were measured using an enzyme-linked chemiluminescent immunoassay. The diagnostic accuracy was analyzed using the receiver operating characteristics (ROC) curve. RESULTS: Plasma GPC3 levels in HCC patients were very low (0–3.09 ng/mL) in Assay 1, while only 3 of the 157 patients (1.9%) showed detectable GPC3 levels in Assay 2. The median GPC3 level was not significantly elevated in the HCC group (0.80 ng/mL) compared with the LC group (0.60 ng/mL). The area under the ROC curve (AUC) for GPC3 was 0.559 in Assay 1. In contrast, the median AFP level was significantly higher in HCC (27.72 ng/mL) than in LC (4.74 ng/mL), with an AUC of 0.729. CONCLUSION: The plasma level of GPC3 is a poor diagnostic marker for HCC, being far inferior to AFP. The development of a consistent detection system for the blood level of GPC3 is warranted.

Evaluation of serum glypican-3 and a-fetoprotein levels in patients with liver cirrhosis and hepatocellular carcinoma

Hepatocellular carcinoma [HCC] is one of the most common malignant tumors. HCC occurs mainly in patients with chronic liver disease such as in hepatitis B and C infection. HCC lesion of one cm in diameter with high or low echogenicity can be detected by ultrasonography and confirmed by liver needle biopsy, however, it is still very difficult to detect small isoechogenic HCC lesions especially when a-fetoprotein [AFP] is normal. The serum level of Glypican-3 [GPC-3] has been reported as a marker of HCC. The aim of our study was to evaluate the diagnostic value of serum [GPC-3] and a-AFP in patients with liver cirrhosis and HCC. All patients were subjected to full history taking, clinical examination, laboratory investigations, abdominal ultrasonography and ultrasonography guided percutaneous liver needle biopsy. To evaluate the role of [GPC-3] in the diagnosis of HCC, we simultaneously studied serum [GPC-3] and [AFP] levels in 40 patients with cirrhosis, 40 patients with HCC and 40 healthy subjects as a control. Serum [GPC-3] in patients with HCC [563 +/- 220ng/ml] and in cirrhotic patients [275 +/- 153 ng/ml] was significantly higher than control [206 +/- 127 mg/ml p<0.001] with 300 ng/ml [mean value of controls plus 2 standard deviations] considered as the cut-off point. [GPC-3] was more sensitive [86 vs 65%] but less specific [80.5 vs 90.9%] than [AFP] at level of > 400 ng/ml as a tumour marker of HCC. We conclude that [GPC-3] is useful marker, in conjunction with [AFP] and liver ultrasonography for detecting HCC

Clinical values of AFP, GPC3 mRNA in peripheral blood for prediction of hepatocellular carcinoma recurrence following OLT

Hepatocellular carcinoma [HCC] is one of the most common malignancies worldwide. Annually, about 200,000 patients died of HCC in China. Liver transplantation [LT] holds great theoretical appeal in treating HCC. However, the high recurrence rate after transplantation is the most important limiting factor for long-term survival. To assess the value of alpha-fetoprotein [AFP] messenger RNA [mRNA], Glypican-3 [GPC3] mRNA-expressing cells in the peripheral blood [PB] for prediction of HCC recurrence following orthotopic liver transplantation [OLT]. 29 patients with HCC who underwent OLT with a minimum clinical follow-up of 12 months were included in this retrospective study. We detected APF mRNA, follow-up of 12 months were included in this retrospective study. We detected AFP mRNA, GPC3 mRNA-expressing cells in the PB by TaqMan real-time reverse transcriptase-polymerase chain reaction [RT-PCR], pre-, intra- and post-operatively. The early recurrence of patients was evaluated. 8 [285], 15 [52%], and 9 [31%] patients had AFP mRNA detected pre-, intra-, and post-operatively, respectively. With 12 months of follow-up, HCC recurred in 7 [24%] patients. Univariate analysis revealed that positive pre- and post-operative AFP mRNA, TNM stage as well as vascular invasion were significant predictors for the HCC recurrence. Multivariate analysis revealed that being positive for AFP mRNA pre-operatively remained a significant risk factor for HCC recurrence after OLT. GPC3 mRNA was expressed in all PB samples. There was no significant difference in the expression levels of GPC3 mRNA between the HCC and control groups. There were no significant differences in GPC3 mRNA expression values between those patients with and without tumor recurrence. The pre-operative detection of circulating AFP mRNA-expressing cells could be a useful predictor for HCC recurrence following OLT. GPC3 mRNA - expressing cells in PB seem to have no diagnostic value

Glypican 3 amino terminal marker for early detection of hepatocellular cacinoma

HCC is the 5[th] common cancer worldwide. Due to global increase of hepatitis B and C infection, the incidence of hepatocellular carcinoma [HCC] has been steadily increasing. The seroprevalence of HCV in Egypt is currently between 20 -35%. Because Alfa Feto protein [AFP] has limited sensitivity for small hepatocellular carcinoma foci, Glypican-3 [GPC-3] oncofetal protein which is over expressed in HCC could represent a hope for early detection. Evaluating the validity of Glypican-3 as an early detector of HCC. 10 healthy controls and 40 HCV positive patients distributed as follows: 10 patients with chronic hepatitis C virus infection [CH], 10 patients with compensated cirrhosis [CC], 10 patients with decompensated cirrhosis [DC] and 10 patients with HCC. Liver functions: ALT, AST, Bilirubin [T], Albumin, gamma GT. Tumor markers: AFP and GPC-3.Viral markers: HCV antibodies, HBs Ag and HBc Ab. AFP mean was126 ng/ml and GPC-3 mean was 34.63 ng/ml in HCC group which were significantly higher than the other studied groups. No significant correlation was found between AFP and GPC-3.The area under ROC of GPC-3 was higher than AFP suggesting increased GPC-3 sensitivity. AFP showed sensitivity of 70% in HCC, 30% in D.C and 20% in C.C with 100% PPV, also AFP had 100% specificity with low NPV compared to GPC-3. GPC-3 was detected in all HCC groups, DC and CH showing 100% diagnostic performance. GPC-3 in C.C revealed 70% sensitivity with 100% PPV and 100% specificity with low NPV. GPC-3 was elevated in context of patients with CH, CC and DC as it is an oncofetal protein produced by regenerating liver cells. GPC-3 and AFP improve the prediction accuracy of HCC in those seronegative to AFP