The potential value of plasma Circ-ITCH in hepatocellular carcinoma patients with current hepatitis C virus infection.

BACKGROUND: There is an obvious need to diagnose hepatocellular carcinoma using novel non-invasive and sensitive biomarkers. Circular RNAs have recently attracted great interest as promising biomarkers and treatment targets. However, their function in hepatocellular carcinoma whose etiology related to hepatitis C has been rarely studied. AIM OF WORK: The current study was conducted to analyze differential expression of circ-ITCH in plasma of Egyptian HCC patients with concomitant HCV infection, compared to normal control subjects, to investigate its correlation with liver function parameters, and to determine the possible diagnostic ability of circ-ITCH in plasma as a non-invasive marker, compared to its linear counterpart. RESULTS: The results showed that the relative expression of circ-ITCH was significantly higher in the plasma of HCC patients (P<0.05). Moreover, when comparing its expression in the metastatic and non-metastatic subgroups, it was significantly higher in the non-metastatic HCC group compared to control group (P<0.05). Circ-ITCH was positively correlated with liver enzymes AST, ALT (P<0.001), also was significantly higher in HCC child C patients. To evaluate the potential diagnostic value of circ-ITCH in plasma, a ROC curve was generated, the AUC was 0.661, (95% CI: 0.5433-0.778) with a sensitivity and specificity 65% and 70% respectively. CONCLUSION: The results revealed that circ-ITCH is-with no doubt-involved in the pathogenesis of HCC and its high level may be related to HCV infection, further researches in this area will certainly make great contributions in understanding. In conclusion our results suggested that circ-ITCH may be used as a noninvasive diagnostic marker and a promising therapeutic target for HCC.

Soluble VEGF/sFLt1 ratio is an independent predictor of AML patient out come.

Angiogenesis is the formation of new blood vessels and is controlled by a balance between positive and negative angiogenic regulatory factors. Soluble vascular endothelial growth factor receptors 1,2 (Flt-1, KDR) are the negative counterpoint to the vascular endothelial growth factor (VEGF) signaling pathway, which has been characterized as one of the most important endothelial regulator in human angiogenesis. In the present work, we tested the differential prognostic relevance of soluble vascular endothelial growth factor (VEGF), their receptors 1 (Flt-1), 2 (KDR), and the ratio between sVEGF/sFlt-1 in 43 patients with acute myeloid leukemia (AML). sVEGF and its soluble receptors were assessed using an ELISA. Soluble VEGF, sFLT-1 and sKDR concentration levels were significantly higher in AML patients at diagnosis when compared to the levels in normal controls. sVEGF, sFlt1 and the sVEGF/sFlt1 ratio were significantly higher in non responders when compared to responders (P < 0.001 for all). However, there was no significant difference regarding sKDR levels (P > 0.05). sVEGF, the sVEGF/sFlt1 ratio but not sFlt1 and sKDR levels were significantly elevated in those who did not survive, when compared to survivors. sVEGF, sFlt1 levels were significantly correlated to WBC counts (R = 0.93, P = 0.000, R = 0.56, P = 0.000, respectively); bone marrow blast cell counts (R = 0.92, P = 0.000; R = 56, P = 0.000, respectively); peripheral blood blast cell counts (R = 0.91, P = 0.000; R = 0.52, P = 0.000, respectively); sKDR was only correlated to peripheral blood blast cell counts(R=0.37,P=0.014). Cox regression analysis results with sVEGF, sFlt1, sKDR, sVEGF/sFlt1 ratio suggest that the most important predictor for AML outcome is the sVEGF/sFlt1 ratio. In conclusion, sVEGF/sVEGF ratio is independent predictor of AML patient out come, and its significance should be assessed when considering antiangiogenic therapy.