Circulating microRNA-301 as a promising diagnostic biomarker of hepatitis C virus-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a serious consequence of persistent hepatitis C virus (HCV) infection and represents one of the most aggressive neoplasms globally. The implication of microRNA-301 (miR-301) in the initiation and progression of different types of cancers has been proved. We aimed to assess circulating microRNA-301 as possible biomarker for the early detection of HCC in patients with chronic HCV infection. miR-301 expression levels were estimated in plasma samples of 42 patients with newly diagnosed HCV-related HCC, 48 chronically HCV infected patients with liver cirrhosis and 40 healthy individuals by reverse transcription-quantitative polymerase chain reaction technique. In comparison with chronically HCV infected patients and healthy controls, miR-301 expression levels were significantly increased in HCC patients (P < 0.001). miR-301 levels distinguished HCC patients from chronic HCV patients, with area under the receiver-operating characteristic curve of 0.89 (95% CI 0.82-0.96), the sensitivity and the specificity were 78.57% and 89.58% respectively. Moreover, miR-301 levels were significantly linked with tumor size (P = 0.014), serum levels of alpha-fetoprotein (AFP) (P = 0.028) and Barcelona Clinic Liver Cancer (BCLC) score (P = 0.003). These results reveal that miR-301 can serve as a promising non-invasive biomarker for diagnosis of HCC in chronically HCV infected patients.

Erythroferrone and iron status parameters levels in pediatric patients with iron deficiency anemia.

OBJECTIVES: To investigate the link between serum erythroferrone (ERFE) levels and iron status parameters in pediatric patients with iron deficiency anemia. METHODS: The study consisted of 66 children (36 with iron deficiency anemia and 30 healthy age- and gender-matched controls) who were investigated for serum levels of iron, total iron-binding capacity (TIBC) using automated chemistry analyzer, serum ferritin using electrochemiluminescence immunoassay and ERFE by specific enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: Serum erythroferrone levels in iron deficiency anemia patients (191.55 ± 83.74 pg/mL) were significantly higher than those in control group (42.22 ± 16.55 pg/mL) (P < .001). In iron deficiency anemia patients, serum erythroferrone concentrations correlated negatively with hemoglobin concentration (r = -.39; P = .01), serum iron (r = -.63; P < .001), transferrin saturation (r = -.66; P < .001), and serum ferritin (r = -.46; P = .004) while positive correlation was observed between serum erythroferrone concentrations and TIBC (r = .62; P < .001) CONCLUSION: The newly identified erythroferrone hormone may act as physiological hepcidin suppressor in cases with iron deficiency anemia, and so it may serve as a specific promising target of therapy in such cases.

LncRNA CRNDE is downregulated and associated with poor prognostic markers in chronic lymphocytic leukemia.

INTRODUCTION: Chronic lymphocytic leukemia (CLL) is characterized by a very heterogeneous clinical outcome. Thus, a plethora of prognostic factors and systems has been identified to place patients into different risk categories and to guide therapy decisions. The classic clinical staging models by Rai and Binet have been the cornerstone of patient management for several years. The greater insight into the molecular biology of CLL facilitated the advent of prognostic genetic biomarkers that are expected to impact clinical practice soon in the future. Therefore, we aimed to investigate the expression of long non-coding RNA (lncRNA) CRNDE in patients with CLL, and to analyze its relationship with the clinicopathological parameters of CLL. METHODS: In this study, 40 untreated CLL patients and 30 age- and gender-matched controls were enrolled. The analysis of lncRNA CRNDE expression was determined using reverse transcription-quantitative polymerase chain reaction technique. RESULTS: Our result confirmed the downregulated expression of LncRNA CRNDE in CLL patients compared to controls (p < 0.001). The low expression of CRNDE was significantly associated with poor prognostic markers including advanced stage of CLL, high levels of serum beta-2 microglobulin and lactic dehydrogenase, and the presence of del17p (p = 0.029, p = 0.013, p = 0.003, p = 0.028; respectively). CONCLUSION: Our study demonstrated that LncRNA CRNDE is significantly downregulated and associated with poor prognostic markers in CLL. It provides a rationale to assess its biological and prognostic impact in CLL.

Changes and correlations of T-cell coinhibitory molecule programmed death-1 and interferon-γ in pediatric immune thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by abnormalities of T cells subsets. Programmed death-1 (PD-1) is a co-signaling inhibitory molecule in T cells that is involved in many autoimmune diseases. PURPOSE: Here we aimed to measure changes in PD-1 expression and serum interferon-γ (IFN-γ) levels before and 1 month after treatment in pediatric patients with newly diagnosed ITP. METHODS: We measured PD-1+ CD4+ T cells percentages using flow cytometry and the serum IFN-γ levels by enzyme-linked immunosorbent assay in 40 pediatric patients with ITP and 20 healthy controls. RESULTS: Compared with healthy controls, the PD-1+ CD4+ T cells percentages and serum IFN-γ levels were significantly higher in ITP patients before and 1 month after therapy. A correlation study revealed that PD-1+ CD4+ T cells percentage was negatively associated with platelet count and positively associated with IFN-γ level in patients with ITP. Furthermore, serum IFN-γ levels were significantly decreased in patients after treatment, but no significant change was detected in the percentage of PD-1+ CD4+ T cells before or 1 month after therapy. CONCLUSION: PD-1+ CD4+ T cells expression and IFN-γ levels were increased in patients with ITP. These preliminary data suggest a potential role of PD-1+ CD4+ T cells as mediators of ITP. We also found a correlation between PD-1+ CD4+ T cells and both platelet counts and IFN-γ levels. These findings suggest a potential role of PD-1+ CD4+ T cells and IFN-γ in the pathogenesis of ITP. Further studies investigating PD-1 expression in different T-cell subsets, serum IFN-γ concentrations, and antiplatelet antibodies levels over a longer duration after therapy initiation could delineate the precise role of PD-1 in ITP pathogenesis. Consequently, novel nontraditional therapeutic strategies for ITP patients may become available.

LncRNA CCAT2 expression at diagnosis predicts imatinib response in chronic phase chronic myeloid leukemia patients.

Long noncoding RNAs (lncRNAs) are identified as key players in the initiation, development, and prognosis of chronic myeloid leukemia (CML). Some lncRNAs are expected to serve as diagnostic biomarkers, predictors of clinical outcomes and therapeutic targets. We aimed to examine the expression of lncRNA colon cancer-associated transcript 2 (CCAT2) in CML patients, as well as to correlate CCAT2 expression with response to imatinib therapy. 43 newly diagnosed patients with chronic phase CML were included, and 30 healthy persons were selected as controls. Real-time reverse transcription PCR was performed to analyze the expression of CCAT2 in peripheral blood mononuclear cells. Our results reported for the first time the upregulated expression of CCAT2 in CML patients as compared with controls (P < 0.001). We demonstrated significant association between CCAT2 expression and therapy response at 3 months, and at 6 months (P = 0.004, and P = 0.005; respectively). Moreover, CCAT2 expression was significantly associated with spleen size (P = 0.006) and EUTOS sore (P = 0.030). LncRNA CCAT2 is highly expressed in the peripheral blood of CML patients, and the enhanced expression at diagnosis is linked to imatinib resistance. CCAT2 is expected to become a reliable molecular marker for predicting imatinib response in chronic phase CML patients.