Serum levels of gamma-glutamyl transpeptidase in relation to HCC human biology and prognosis.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) biomarkers are limited, as even the best studied, alpha-fetoprotein (AFP), is elevated in no more than 50% of HCC patients. The aim was to evaluate several serum liver function tests in relation to survival and tumor characteristics in a large cohort of Turkish HCC patients. METHODS: We retrospectively examined the serum levels of gamma glutamyl transpeptidase (GGT) in relation to patient survival. RESULTS: Kaplan-Meier analysis showed that only GGT and albumin amongst liver function tests, were significantly associated with survival. Survival worsened with increase in GGT levels semi-quantitatively. Increase in GGT levels was also found to significantly correlate with an increase in maximum tumor diameter from 4.5 to 7 cm, a 20-fold increase in serum alpha-fetoprotein level, an increase in tumor multifocality from 20 to 54% of patients, and a doubling in percent of patients with portal vein thrombosis (PVT) from 20 to 40%. Serum GGT levels also showed significant survival differences for patients with low AFP levels. A doublet combination of serum GGT with albumin levels was associated with higher hazard ratios in a Cox regression analysis, as compared with single parameter GGT. The combination parameter pair was also prognostically useful in the low-AFP patient subcohort and was associated with significant differences in patient tumor characteristics. CONCLUSIONS: Serum GGT levels and especially combination serum GGT plus albumin levels, were significantly associated both with HCC patient survival and tumor aggressiveness characteristics, regardless of AFP levels in a large Turkish cohort. This might be especially useful since the majority of HCC patients do not have elevated levels of AFP.

The analysis of lncRNA HOTAIR rs12826786 C>T polymorphism and gastric cancer susceptibility in a Turkish population: lack of any association in a hospital-based case-control study.

BACKGROUND: The HOX transcript antisense intergenic RNA (HOTAIR), a well-known long noncoding RNA (lncRNA), has been widely identified to participate in pathogenesis of multiple cancers. An aberrant up-regulation and biological functions have been observed in gastric cancer (GC). A common single nucleotide polymorphism (SNP) (rs12826786 C>T) at the HOTAIR has been reported to influence HOTAIR expression, but its association with GC has yet to be investigated in Turkish population. AIM: The aim of the present study was to investigate whether HOTAIR rs12826786 C>T polymorphism could be involved in the risk of GC susceptibility in Turkish population. METHODS: We genotyped HOTAIR rs12826786 C>T polymorphism in 312 Turkish individuals including 105 GC patients and 207 healthy controls matched on age and gender by a Real-Time Polymerase Chain Reaction (PCR) with the TaqMan assay. RESULTS: No statistically significant differences were found in the allele or genotype distributions of the HOTAIR rs12826786 C>T polymorphism among GC and healthy control subjects (P > 0.05). CONCLUSIONS: Our results demonstrate that the HOTAIR rs12826786 C>T polymorphism has not been in any major role in genetic susceptibility to gastric carcinogenesis, at least in the population studied here. Independent studies are needed to validate our findings in a larger series, as well as in patients of different ethnic origins.

Relationship between programmed cell death-1 polymorphisms and clearance of hepatitis B virus.

Programmed cell death-1 (PD-1) plays a critical role in regulating T-cell function during hepatitis B virus (HBV) infection. This study investigated the relationship between the polymorphisms of PD-1 gene and the susceptibility to HBV infection. Single nucleotide polymorphisms (SNPs) in PD-1 gene at positions +7146 G>A (guanine to adenine substitution) and +7209 C>T (cytosine to thymine substitution) were analysed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 220 subjects with chronic hepatitis B infection and 165 spontaneous clearance of HBV subjects. However, no statistically significant differences were found in the genotype distributions of the PD-1 +7146 G>A and PD-1 +7209 C>T polymorphisms among chronic hepatitis B and spontaneous clearance subjects. According to stratified analyses, borderline significance was observed between PD-1 +7146 GA genotype and risk of HBV chronicity in the subgroup of male gender (OR = 1.88, 95% 0.95-3.71; P = 0.07). Our findings demonstrate for the first time that the PD-1 +7146 G>A and PD-1 +7209 C>T polymorphisms have not been any major role in genetic susceptibility to chronicity of HBV infection, at least in the population studied here. Independent studies are needed to validate our findings in a larger series, as well as in patients of different ethnic origins.

A functional polymorphism in pre-microRNA-196a-2 contributes to the susceptibility of hepatocellular carcinoma in a Turkish population: a case-control study.

MicroRNAs (miRNAs) are an abundant class of small nonprotein-coding RNAs with posttranscriptional regulatory functions as tumour suppressors and oncogenes. Aberrant expression and structural alteration of miRNAs are thought to participate in tumourigenesis and cancer development. It has been suggested that the presence of single-nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression, and/or binding to target mRNA and represent another type of genetic variability that can contribute to the development of human cancers. Recent studies have indicated that the miR-196a-2 rs11614913 (C→T) polymorphism could alter mature miR-196a-2 expression and target mRNA binding. To determine the association of the miR-196a-2 rs11614913 polymorphism with the risk of hepatocellular carcinoma (HCC) development in a Turkish population, a hospital-based case-control study was designed consisting of 185 subjects with HCC and 185 cancer-free control subjects matched for age, gender, smoking and alcohol status. The genotype frequency of the miR-196a-2 rs11614913 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Our data shows that the CC genotype of the miR-196a-2 rs11614913 polymorphism is associated with increased risk of HCC development in this Turkish population (OR = 2.41, 95% CI: 1.30-4.50, P = 0.005). Furthermore, according to stratified analysis, a significant association was observed between the homozygote CC genotype and HCC risk in the subgroups of male gender (OR = 3.12, 95% CI: 1.53-6.34, P = 0.002) and patients with hepatitis B virus (HBV)-related HCC (OR = 2.88, 95% CI: 1.33-6.22, P = 0.007). Because our results suggest for the first time that the miR-196a-2 rs11614913 polymorphism may be a genetic susceptibility factor for HCC (especially in the male gender and HBV-infected patients) in the Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different ethnic origins.

Chronic hepatitis C responds poorly to combination therapy in chronic hepatis B carriers.

BACKGROUND: The effect of conventional interferon-based therapy of hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection is controversial. Yet, no studies have been carried out into pegylated interferon treatment for chronic HBV/HCV coinfection. We aimed to evaluate the response rate and side effects of conventional or pegylated interferon combined with ribavirin on chronic HBV/HCV coinfection therapy. METHODS: The study included 36 chronic hepatitis patients (M/F: 28/8, mean age 47+/-12 years) who were positive for HBsAg and anti-HCV. They were tested for the presence of HBV-DNA by hybridisation assay, and the samples giving negative results were retested by polymerase chain reaction (PCR). All patients were tested for HCV-RNA using PCR, and the HCV genotype was determined. RESULTS: Nineteen patients were given standard interferon either alone or in combination with ribavirin, whereas 17 were given pegylated interferon and ribavirin combination therapy. None of the patients had HBV-DNA positivity; however, all had HCV-RNA detectable by PCR. All the patients had HCV genotype 1b. The mean alanine aminotransferase and aspartate aminotransferase levels were 118+/-65 U/l and 90+/-95 U/l respectively. Five patients in each group discontinued the treatment due to side effects. Only two patients (one from each group) reached sustained virological response. CONCLUSION: Neither pegylated nor conventional interferon based regimes were effective for HBV/HCV coinfection, in which the dominant virus was HCV. Pegylated interferon and ribavirin therapy was not superior to conventional interferon based regimes in the treatment of HBV/HCV coinfection.