Serum AP-endonuclease 1 (sAPE1) as novel biomarker for hepatocellular carcinoma

Late diagnosis for Hepatocellular Carcinoma (HCC) remains one of the leading causes for the high mortality rate. The apurinic/apyrimidinic endonuclease 1 (APE1), an essential member of the base excision DNA repair (BER) pathway, contributes to cell response to oxidative stress and has other non-repair activities. In this study, we evaluate the role of serum APE1 (sAPE1) as a new diagnostic biomarker and we investigate the biological role for extracellular APE1 in HCC. sAPE1 level was quantified in 99 HCC patients, 50 non-HCC cirrhotic and 100 healthy controls. The expression level was significantly high in HCC (75.8 [67.3\u201387.9] pg/mL) compared to cirrhosis (29.8 [18.3\u201336.5] pg/mL] and controls (10.8 [7.5\u201313.2] pg/mL) (p < 0.001). The sAPE1 level corresponded with its protein expression in HCC tissue. sAPE1 had high diagnostic accuracy to differentiate HCC from cirrhotic (AUC = 0.87, sensitivity 88%, specificity 71%, cut-off of 36.3 pg/mL) and healthy subjects (AUC 0.98, sensibility 98% and specificity 83%, cut-off of 19.0 pg/mL). Recombinant APE1, exogenously added to JHH6 cells, significantly promotes IL-6 and IL-8 expression, suggesting a role of sAPE1 as a paracrine pro-inflammatory molecule, which may modulate the inflammatory status in cancer microenvironment. We described herein, for the first time to our knowledge, that sAPE1 might be considered as a promising diagnostic biomarker for HCC

MicroRNAs as Regulators of Neo-Angiogenesis in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a highly vascularized neoplasm. In the tumor niche, abundant angiogenesis is fundamental in providing nutrients for tumor growth and represents the first escape route for metastatic cells. Active angiogenesis, together with metastasis, are responsible for the reduction of recurrence-free survival of HCC. MicroRNAs (miRNAs) are small non-coding RNAs that have recently drawn attention in molecular targeted therapy or as diagnostic and prognostic biomarkers. MiRNA expression in HCC has been widely studied in the last decade. Some miRNAs have been found to be up- or down-regulated, besides association with apoptosis, metastasis progression and drug resistance have been found. This review article aims to summarize the angiogenetic process in tumor diseases and to update on what has been found in the vast world of HCC-related-miRNAs and, eventually, to report the latest finding on several miRNAs involved in HCC angiogenesis. We searched the state of the arts for the 12 miRNAs found to be involved with angiogenesis in HCC (miR-29b, miR-126-3p, miR-144-3p, miR-146a, miR-195, miR-199a-3p, miR-210-3p, miR-338- 3p, mir-491, mir-497, mir-638, mir-1301) and reported their main molecular targets and their overall effect in the sprouting of new vessels

The Role of Liver and Spleen Elastography in the Screening of Esophageal Varices in Patients with Liver Cirrhosis: Do We Really Need Endoscopy?

Background: recently, the Baveno VI guidelines have suggested that esophagogastroduodenoscopy (EGD) to stage esophageal varices can be avoided in patients with advanced liver disease who have a liver stiffness (LS) 150x103/\u3bcL. Our study aims to analyze spleen stiffness (SS) as a non\u2010invasive method of diagnosis for clinically significant portal hypertension in order to avoid EGD in low\u2010risk patients for esophageal varices. We also want to compare the SS to other non\u2010invasive techniques and analyze their reproducibility and inter\u2010observer concordance. Patients and Methods: in this prospective study, we detected the SS and LS in 150 patients diagnosed with liver cirrhosis to be submitted for endoscopic screening for esophageal varices. In addition, we enrolled 70 healthy control individuals, who for other reasons, had undergone an endoscopic examination of the upper digestive tracts and who were negative for hepatic and lymphoproliferative disease. The discriminatory capacity for the presence of esophageal varices of the SS has been compared with that deriving from other non\u2010invasive procedures (LS, splenic diameter, splenic surface, platelet count, and combined scores deriving from these parameters). Optimal SS cut\u2010offs were sought to exclude the presence of varices. Particular emphasis was placed on the search for possible correlations of the with ultrasound parameters of portal hypertension and platelet count. Finally, we studied in a double\u2010blind fashion inter\u2010operator concordance with 50 measurements for LS, and 25 for SS. Results: cirrhotic patients have significantly higher SS and LS values than controls. The SS values were higher in cirrhotic patients with varices (n = 62) compared to patients without esophageal varices (n = 88) and to healthy controls (p <0.001). SS showed an AUROC of 0.93 (95% C.I., 0.89\u20100.97), statistically different from the other predictors (p <0.001). The cut\u2010off, chosen according to Youden\u2019s Index and equal to 38.55 kPa, showed sensitivity of 87%, specificity of 89%, NPV of 91%, and PPV of 84%. Instead, the cut\u2010off of 30.79 kPa has 100% sensitivity and 100% NPV. The cut\u2010off of 69.73 kPa demonstrated specificity and PPV of 100%. The SS demonstrated weak linear correlation with the splenic dimensions (bipolar diameter and surface measured at the organ\u2019s hilum). Moreover, it has a linear correlation with the platelet count, which was greater than that present with LS (r = 0.5 vs r = 0.32). The test revealed an excellent intraclass correlation coefficient (ICC) equal to 0.96 for SS and 0.97 for LS. Conclusion: the results of this study show how the SS can play an important role in the daily clinical management of cirrhotic patients. The SS (alone or combined with other indicators) may play an important role as a non\u2010invasive screening test for predicting the risk of varices