Clinical Significance of MiR-130b and MiR-125b as Biomarkers in Hepatocellular Carcinoma.

OBJECTIVE: This study aimed to assess the role of miR-130b and miR-125b expression in Hepatocellular Carcinoma (HCC) progression. SUBJECTS AND METHODS: This study was carried out on 150 subjects classified into three groups: Group I, 50 healthy controls; Group II, 50 patients with liver cirrhosis; Group III, 50 patients with HCV related HCC. The controls were frequency matched based on age and sex with the other groups. All individuals were subjected to testing for liver function, alpha-fetoprotein (AFP), and viral markers. miR-130b and miR-125b were detected in plasma using a quantitative real-time RT-PCR. RESULTS: miR-130b was significantly upregulated, whereas miR-125b was significantly downregulated in HCC patients compared with cirrhotic patients and healthy controls. There was a significant correlation between miR-130b and AFP and tumor size. Receiver operating curve (ROC) analyses suggested that plasma miR-130b had a significant diagnostic value for HCC with a sensitivity of 92% and a specificity of 77.5%.  A sensitivity of 85.5% and a specificity of 82.5% was observed for  miR-125b for HCC. CONCLUSION: Plasma miR-130b and miR-125b may play a role in disease progression and development of HCC and may act as potential biomarkers for the diagnosis of HCC.

ESR1 gene polymorphism (rs827421) as a potential genetic marker for constitutional delay of growth and puberty in Egyptian adolescents.

Constitutional delay of growth and puberty (CDGP) is a variant of normal pubertal timing and progress. It is the most common form of delayed puberty in both genders. The genetic director of CDGP is ill-understood despite the positive family history result noted in those patients. The current study aimed at assessing the role of estrogen receptor 1 (ESR1) gene variant (rs827421) in Egyptian adolescents with CDGP. A cross-sectional study with follow-up part was carried out on 6760 children aged 4 to15 years. The study focused generally on children aged 13-15 years in order to evaluate the prevalence of delayed puberty in relation to all ages in general and to their peers in specific. Assessment of serum TSH, FSH, and LH was conducted on all participants, along with the measurement of serum-free testosterone for males and estradiol for females. Genotyping of ESR1 (rs827421) was done to all subjects through the use of TaqMan discrimination assay by real-time PCR. ESR1 (rs827421) GG genotype and G allele were significantly dominant among CDGP adolescents in comparison with controls (OR = 25.67 and 6.90). As regards follow-up of testicular size, AA genotype was significantly associated with increased size in the right and left testis compared to other genotypes (P = 0.021 and 0.006, respectively). Moreover, AA genotype showed significantly higher Tanner stage in both males and females in comparison with other genotypes. Serum estradiol level was significantly higher in AA genotype group than other genotypes groups. ESR1 gene polymorphism can be considered a potential genetic marker for CDGP in both sexes in a sample of Egyptian adolescents.

Role of Adiponectin Gene and Receptor Polymorphisms and Their mRNA Levels with Serum Adiponectin Level in Myocardial Infarction.

BACKGROUND AND AIM: Genetic factors are vital participants in the development and progression of myocardial infarction (MI). Adiponectin has been assumed to have a protective role in MI and adiponectin receptors variants could be a determinant for atherosclerosis. We aimed to evaluate the prevalence of ADIPOQ (rs2241766) and ADIPOR2 (rs10773989) polymorphisms and their association with mRNA levels and circulatory adiponectin levels in patients with MI. SUBJECTS AND METHODS: A total of 220 participants were classified into two groups: group 1 included 120 patients with MI, and group 2 involved 100 healthy participants as controls. Genotyping of ADIPOQ (rs2241766) and ADIPOR2 (rs10773989) polymorphisms were analyzed using an allele discrimination assay with real-time PCR and their relative expression or mRNA levels were determined by real-time PCR. Serum adiponectin level was determined using an ELISA technique. RESULTS: The ADIPOQ rs2241766 GG genotype and G allele and the CC genotype and C allele of ADIPOR2 rs10773989 were significantly prevalent in patients with MI and associated with increased risk of MI. We detected a marked reduction in serum adiponectin, ADIPOQ and ADIPOR2 mRNA levels in patients than control. The GG genotype of ADIPOQ rs2241766 and the CC genotype of ADIPOR2 rs10773989 had the lowest levels of their mRNA and adiponectin level in both patients and controls. CONCLUSION: Adiponectin gene and receptor variants are potentially related to MI risk; furthermore, their expressions were markedly depressed in MI which suggests their use as potential biomarkers for MI.

Diagnostic Performance of microRNA-122 and microRNA-224 in Hepatitis C Virus-Induced Hepatocellular Carcinoma (HCC).

Background and objectives: Hepatocellular carcinoma (HCC) is a potential health problem in Egypt because of the high prevalence of HCV infection. Using alpha-fetoprotein for diagnosis is unsatisfactory especially in early stages. Many studies showed that microRNAs (miRNA) expression may be associated with the development and progression of various types of cancer including HCC and it may serve as biomarkers for diagnosis. This study examined two miRNAs which are miRNA-122 and miRNA-224 if it could serve as biomarkers for diagnosis of HCC. Methods: This study included 20 patients with HCV-induced HCC and 20 patients with HCV-induced liver cirrhosis for comparison. As well as 20 healthy volunteers as controls. All participants were subjected to history taking, clinical examination, and determination of serum alpha-fetoprotein. Quantification of plasma miRNA-122 and miRNA-224 was done by real-time quantitative PCR. Results: Our results showed that levels of miRNA-122 were significantly lower in HCC group compared to the cirrhosis group and controls, while levels of miRNA-224 were significantly higher. The levels of both miRNAs have a correlation with tumor size. Moreover, the diagnostic accuracy of miRNA-122 (sensitivity 95%, specificity 81%, p-value <0.001) and of miRNA-224 (sensitivity 85%, specificity 79%, p-value <0.001) in discriminating patients with HCC from patients with liver cirrhosis were higher than that of alpha-fetoprotein (sensitivity 70%, specificity 70%, p-value <0.05). In addition, combining any one of these miRNAs with alpha-fetoprotein will increase the diagnostic accuracy compared to using each marker alone. Conclusion: miRNA-122 and miRNA-224 could serve as biomarkers for the diagnosis of HCC.

Value of urinary survivin as a diagnostic marker in bladder cancer.

OBJECTIVE: To study the value of urinary survivin as a diagnostic marker for diagnosis of bladder cancer as compared to urine cytology. STUDY DESIGN: This study was carried out on 40 patients presenting with bladder cancer and 20 patients presenting with benign urological disorders. RESULTS: For bladder cancer diagnosis, urine cytology has lower sensitivity, accuracy, and negative predictive values as compared to survivin, while it has higher specificity and positive predictive value than survivin. On the other hand, the sensitivity, specificity, and the accuracy of combined survivin and urine cytology were 100%, 95% and 97%, respectively. Positive urine cytology and survivin were significantly higher in cases showing advanced stage and high grade as compared to cases presented with superficial stage and low grade. CONCLUSION: Urinary survivin appears to be a reliable, noninvasive diagnostic test to identify patients with bladder cancer. The sensitivity of survivin test was superior to that of urine cytology in the diagnosis of bladder cancer, especially in cases presenting with superficial stage or low grade. Combined evaluation of both survivin and urine cytology gave better sensitivity, specificity, and accuracy for bladder cancer diagnosis.