Objective: Genome-wide association studies (GWAS) have identified a number of genetic variants associated with the susceptibility of bladder cancer (BC) in European and Chinese populations. Here, we assessed the association of two of these variants, rs9642880 and rs710521 in an Egyptian patients and also examined the expression of c-Myc. The basis was due to the absence of studies on Egyptian patients to determine the association between rs9642880& rs710521 and bladder cancer risk, particularly due to the known role of the variant (rs9642880) in the Progression and development of bladder cancer. Methods: Urine samples were collected from onehundred and fiftybladder cancer patients under particular standards and fifty healthy controls. Genomic DNA was extracted, rs9642880 G>T and rs710521 A>G polymorphisms were amplified, assessed via restriction fragment length polymorphism(RFLP) and sequenced. Urine retrieved results were compared to the histopathological diagnosis of tissue biopsies and to the results of C-Myc immunohistochemistry. Data were statistically analyzed using Microsoft Excel 2016, association between significant genotypes of the two studied variables and bladder cancer risk was performed. Results: We found that the TT genotype of rs9642880 G>T was strongly associated with the risk of bladder cancer, andfor rs710521 A>G, AG genotype was also identified to has an association with bladder cancer risk.All 150 tumor sections showed positive immunoreactivity for c-Myc in the nucleus and the cytoplasm. Conclusion: Identifying the association to risk of bladder cancer using genetic analysis will help in the early detection of the disease.
Objective: Hepatocellular carcinoma (HCC) accounts for more than 80% of primary liver cancers. Moreover, in the next 10 years, more than one million patients are expected to die from liver cancer as estimated by the World Health Organization. The aim of the present study is to define the microsatellite phenotype in the blood, tumor and nontumor tissue samples from hepatocellular carcinoma cases to develop a simple non-invasive method for diagnosis and detection of the disease. Methods: A total of 100 patients with histologically-proven HCC were enrolled in this study, blood samples and tissue specimens from tumor and nontumor tissue were obtained from each patient. DNA was extracted and microsatellite instability MSI status was determined by polymerase chain reaction (PCR) using 5 mononucleotide and 5 dinucleotide repeats. Results: Among the 100 HCC tumors analyzed, (8%) considered as displaying a typical MSI-H phenotype as defined by instability in at least 3 of the 10 repeats analyzed, (61%) tumors displayed MSI-L and (31%) displayed MSS while in plasma the instability was (40%) for MSI-H, (44%) for MSI-L and (16%) for MSS. Conclusion: our findings could point to the achievement that HCC patients could be diagnosed by MSI analysis using blood sample as non-invasive way and this conclusion achieved our aim as the study shows impressive and promising results.
BACKGROUND: Mutation signatures contributing to the tumorigenesis of bladder cancer (BC) are complex and heterogeneous, resulting in unpredictable progression, recurrence, and time survival. Clinically, useful prognostic and predictive biomarkers for both disease recurrence and surveillance are therefore needed. Activating fibroblast growth factor receptor 3 (FGFR3) mutations are regarded as early drivers in the molecular pathogenesis of BC. AIM: The aim of the present study is to evaluate the frequency and distribution pattern of FGFR3 mutation in urine sediments of BC patients in relation to its immunohistochemical (IHC) and molecular expression and to determine the prognostic and predictive value of FGFR3 relative to BC. PATIENTS AND METHODS: One hundred and sixty patients with diagnosed BC and 80 healthy controls were recruited. Urine samples were collected from all participants. DNA was extracted and FGFR3 mutations were examined in exons 7, 10, and 15 by polymerase chain reaction. IHC for FGFR3 expression and fluorescence in situ hybridization technique for assessment of gene amplification was also applied in tissue sections. RESULTS: Ninety-eight (61.3%) patients were mutant in exon 7, 82 (51.3%) were mutant in exon 10, while only 14 (8.8%) were mutant in exon 15. Univariate logistic regression analysis revealed that mutations in the three exons of FGFR3 were statistically associated with BC and could be used as predictor and/or prognostic parameters for BC. Receiver operating characteristic analysis showed that the mutation of exons 7 and 10 could be used as diagnostic biomarkers for BC. Our findings confirm that FGFR3 mutations are associated with tumors of low grade and stage. The prevalence of mutations was significantly associated with recurrence and survival time of patients for all exons. Kaplan–Meier analysis revealed a significant association between mutant patients in exon 10 and survival time. Our findings suggest that estimation of FGFR3 expression and gene amplification could serve as a prognostic indicator in the follow-up of BC patients. It could also be utilized for molecular targeted therapy in BC. CONCLUSION: Our data confirmed the feasibility of FGFR3 mutation detection in urine sediment. FGFR3 genetic mutations are independent prognostic factors for tumor recurrence and the genetic alternation of FGFR3 could be used for prediction of survival time of BC patients.
Background: Hepatocellular carcinoma (HCC) accounts for more than 80% of primary liver cancers. Moreover, in the next 10 years, more than one million patients are expected to die from liver cancer as estimated by the World Health Organization. The aim of the present study is to evaluate the clinical utility of using Glypican (GPC3), Vascular endothelial growth factor (VEGF) and Golgi protein 73 (GP73) in serum by Enzyme-Linked Immunosorbent Assay (ELISA) and by Real-Time Polymerase Chain Reaction (RT-PCR), as diagnostic markers to differentiate HCC from cirrhotic liver disease. Methods: A total of 50 patients with histologically-proven HCC, 50 liver cirrhosis patients and 20 healthy volunteers as controls were enrolled in this study, blood samples were obtained from each patient. Expression of the studied biomarkers was evaluated by ELISA and Real-Time PCR. Results: Statistical analysis of RT-PCR results showed that the expression of GPC3, VEGF and GP73 in serum of patients with HCC was significant (P value < 0.001, 0.01, and < 0.001) respectively and increased when compared to the cirrhotic group. Furthermore, the serum protein levels of GPC3 and VEGF in HCC and cirrhotic patients were significant when compared to the control group. While no significance was found between HCC and cirrhotic group. The serum protein level of GP73 was significantly increased in HCC and cirrhosis groups compared to the control group (P value < 0.001). Moreover, a significant increase was evident in HCC group compared to cirrhotic group (P value < 0.001). The results of the present study showed that the combination of VEGF and GP73 could discriminate HCC from cirrhosis. Conclusion: GPC3, VEGF and GP73 are reliable biomarkers for diagnosis of HCC. The serum level of GP73 is a potential screening marker for discriminating HCC from liver cirrhosis.
Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease. Hepatocellular carcinoma (HCC) is a major complication associated with HCV virus infection, with significant mortality and morbidity rates. This study aimed to measure biochemical liver parameters and HCV RNA levels for detection the severity of hepatitis C virus-associated hepatocellular carcinoma. The study was conducted on 100 patients, with ages ranging from 36 to 68 years and patients grouped into four groups. The 1 st group served as control group (n= 25),the second group (n=25): Hepatitis C Virus, the third group (n=25): HCV-associated HCC and the fourth group (n=25): After HCC removal and tumor resection. Serum samples were collected from the studied patients. Liver function enzymes (ALT, AST, Alkaline phosphatase) and another function parameters (Albumin and Total bilirubin) were tested to all patients of the studied groups. The results showed that hepatitis C Virus, HCV-associated HCC, and after HCC removal groups had an increase in liver function enzymes, decrease in albumin levels, and an increase in total bilirubin levels which indicate damage in the liver. Viral loads indicated in males infected higher than in females and significantly 98 MOHAMED EBEID et al. increased in HCV patients, and a highly significant increase in HCV associated HCC patients. Conclusively, Hepatitis C Virus, HCV-associated HCC, and After HCC removal groups had an increase in liver function enzymes, decrease in albumin levels, and an increase in total bilirubin levels which indicate damage in the liver. Viral loads indicated in males infected higher than females are significantly increased in HCV patients, and a highly significant increase in HCV associated HCC patients.
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