No abstract

Aim of the studyThe diagnosis of hepatocellular carcinoma (HCC) is usually late, due to the lack of early detection of biomarkers for HCC. Metabolomics analysis has emerged as a useful tool for studying human diseases. The objective of the study was to investigate the differences in plasma metabolites between hepatitis C virus (HCV)-induced cirrhosis and HCC.Material and methods22 subjects with HCV-related liver cirrhosis and 22 subjects with HCC were enrolled. Clinical, routine laboratory and imaging studies were done. Gas chromatography/mass spectrometry (GC/MS) was used for metabolomics analysis of patients’ plasma samples.Results34 known metabolites were detected, of which five metabolites were identified to have the strongest discriminatory power for separation between HCC and cirrhosis groups: octanoic acid (caprylic acid), decanoic (capric acid), oleic acid, oxalic acid and glycine. These are 3 fatty acids (FA), a dicarboxylic acid and a glucogenic amino acid, respectively. No significant correlation was found between the relative intensities of the five metabolites and any of the patient or tumor characteristics (Child-Turcotte-Pugh (CTP) score, Barcelona Clinic Liver Cancer (BCLC) stage, number of focal lesions and size of largest focal lesion). ROC curve analysis was performed and area under the curve (AUC) was calculated, revealing that oleic acid, octanoic (caprylic) acid and glycine had higher positive predictive value than α-fetoprotein.ConclusionsThe study of metabolomics (particularly involving FA) may help define distinct metabolic patterns to distinguish HCV-induced liver cirrhosis from HCC patients. Future research in this field is still needed, particularly concerning HCC treatment strategies which target fatty acid-related metabolic pathways.

Aim of the study: Micro-ribonucleic acids (miRNA) are small single stranded RNA molecules. They act as key regulators of several cellular processes such as proliferation, apoptosis, tumor differentiation, invasion and metastasis. Hepatocellular carcinoma (HCC) represents the most common primary liver cancer. miRNA-224 is an oncomiR that is highly upregulated in HCC tissues. The aim of the present study was to measure the relative expression of circulating miRNA-224 in the serum of patients with HCV-related liver cirrhosis and HCC and to assess its usefulness in the diagnosis of HCC. Material and methods: Forty-eight patients were classified into two groups: 24 HCV-related HCC patients (HCC group), and 24 HCV-related liver cirrhosis patients (LC group). A third group included 24 healthy volunteers (control group). Clinical examination, imaging studies and routine laboratory investigations, including serum α-fetoprotein (AFP), were done. Quantification of serum miRNA-224 expression was performed using real time reverse transcription polymerase chain reaction (RT-PCR). Results: The relative expression of serum miRNA-224 was significantly higher in HCC patients compared to LC patients and healthy control subjects. Its level correlated positively with the serum concentration of AFP and with Barcelona Clinic Liver Cancer (BCLC) stage of HCC. By combining miRNA-224 relative expression with AFP, their diagnostic sensitivity, specificity and accuracy increased significantly (95.0%, 92.1% and 93.2%, respectively) compared with either of the two markers alone in discriminating HCC from liver cirrhosis. Conclusions: Serum miRNA-224 relative expression may aid in the diagnosis of HCC. Better diagnostic performance is obtained if miRNA-224 is combined with other tumor markers such as AFP.

Introduction:Over the past three decades, the number of people with diabetes mellitus (DM) has more than doubled globally, making it one of the most important public health challenges to all nations. Aldose reductase (AR) is a rate-limiting enzyme in the polyol pathway, which has been implicated in the pathogenesis of diabetic microvascular complications; however, the association of the AR gene with diabetic macrovascular complications has rarely been investigated.Aim:The study aimed to identify the possible association between C(-106) T polymorphism of the AR gene and diabetic macroangiopathy in a cohort of Egyptian patients with type 2 DM.Settings and Design:This study was conducted on 100 Egyptian subjects, the control group (n = 20) and the patient group (n = 80) with type 2 diabetes which were further subdivided into two subgroups with (n = 48) and without macroangiopathic complications (n = 32) as evidenced by carotid intima-media thickness, electrocardiography (ECG) ischemic changes, cerebrovascular insufficiency, and peripheral vascular insufficiency.Subjects and Methods:All studied subjects were subjected to detailed history taking, clinical examination, ECG, carotid ultrasonography, routine laboratory investigations, and molecular studies including the detection of AR C(-106) T gene polymorphisms using the polymerase chain reaction (PCR)/restriction fragment length polymorphism technique.Results:The genotype distribution and allele frequency of AR C(-106) T showed no statistical significance also the genotypes were not associated with any of the different studied parameters.Conclusions:The results suggest that the C(-106) T polymorphism in the AR gene is not involved in the pathogenesis of macroangiopathy in type 2 diabetes.

Background: Breast cancer is a disease characterized by progressive genetic abnormalities including mutations in tumor suppressor genes and oncogenes, as well as other chromosomal abnormalities. Protein inhibitor of activated signal transducer and activator of transcription 3 (PIAS3) is a member of the PIAS family of transcriptional modulators; its expression is altered in many cancers. Micro-ribonucleic acid (miRNA)-18a acts as an oncogene by negatively regulating PIAS3 and thus modulating the expression of signal transducer and activator of transcription 3 (STAT3) target genes. The aim of this work is to examine the expression levels of PIAS3 gene and miRNA-18a in breast cancer tissues and nearby non-tumor tissues. The samples of breast cancer and paired samples of noncancerous tissue from the same resected breast were obtained from 25 patients undergoing surgery. Full history taking, complete physical examination, pre-operative fine-needle aspiration cytology or ultrasonic (U/S)-guided core biopsy from the breast mass, final surgical biopsy for pathological examination, and routine laboratory investigations were done. Estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) status were evaluated. Total RNA extraction followed by real-time reverse transcriptionpolymerase chain reaction (RT-PCR) for quantification of PIAS3 mRNA and miRNA-18a expressions was performed. Results: The mean value of PIAS3 mRNA fold expression was significantly lower in the tumor group (5.12 ± 9.85) compared to the normal group (8.38 ± 17.10) (p = 0.040). miRNA-18a fold expression was higher among tumor group (3.5 ± 7.4) than that of normal group (2.5 ± 3), however, it did not reach the level of statistical significance (p = 0.861). miRNA-18a fold expression had negative significant correlation with PIAS3 mRNA fold expression (p = 0.018). A significant association was observed between miRNA-18a expression in breast cancer tissues and the pathological grade of the tumor (p = 0.029). Conclusions: The results of this study showed that PIAS3 mRNA and miRNA-18a might be of importance in breast cancer development and pathogenesis, and this may be reflected on the treatment strategies targeting STAT3 pathway. However, further studies with larger sample size are needed to validate these observations.