miRNA Signature of Hepatocellular Carcinoma Vascularization: How the Controls Can Influence the Signature

Abstract

Our data confirm that the choice of the methodology, and particularly the control used for normalization, represents the main concern in miRNA evaluation, particularly in a heterogeneous model such as liver pathology. Still we observed the deregulation of some common miRNAs as promising in HCC cancerogenesis and progression. A standardized control will be a crucial achievement to compare miRNA expression among different laboratories.

Immunomorphology and molecular biology of mixed primary liver cancers: is Nestin a marker of intermediate‐cell carcinoma?

“…Since 2012 we have observed that Nestin protein was mainly expressed in endothelial cells of activated arteries/arterioles andin HCCin intratumoral sinusoids and neoarteries, but never in neoplastic hepatocytes. 16,17 Of note, two papers in the literature described Nestin expression in hepatocytes in a percentage of HCC 11,15 ; in our experience using the monoclonal antibody anti-Nestin clone 10C2, we never observed Nestin expression in hepatocytes. This negative pattern is in keeping with that reported in the Human Atlas with another four clones of anti-Nestin antibody (https://www.proteina tlas.org/ENSG00000132688-NES/pathology).…”

“…found tissue Nestin expression significantly increased in HCC resistant to chemotherapy and with poor survival . It is noteworthy that in our experience HCC expresses Nestin only in the endothelial cells of sinusoids and neoarteries, but not in neoplastic hepatocytes …”

“…The Nestin protein has been demonstrated to be a marker of immature/stem cell‐like populations in various tissues, such as brain, arterial vasa vasorum and liver. Since 2012 we have observed that Nestin protein was mainly expressed in endothelial cells of activated arteries/arterioles and – in HCC – in intratumoral sinusoids and neoarteries, but never in neoplastic hepatocytes . Of note, two papers in the literature described Nestin expression in hepatocytes in a percentage of HCC; in our experience using the monoclonal antibody anti‐Nestin clone 10C2, we never observed Nestin expression in hepatocytes.…”

“…15 It is noteworthy that in our experience HCC expresses Nestin only in the endothelial cells of sinusoids and neoarteries, but not in neoplastic hepatocytes. 16,17 The aim of the present paper was to establish the tissue expression of Nestin in PLC with mixed phenotype (cHCC-CC and intermediate-cell carcinomas) and to correlate the PLC immunoprofile with the gene expression in each tumour component (hepatocellular, cholangiocellular and intermediate).…”

Tissue miRNA 483-3p expression predicts tumor recurrence after surgical resection in histologically advanced hepatocellular carcinomas

“…miR-483-3p expression is heterogeneous across human malignancies, acting as tumorigenic or a tumor-suppressor according to the target [ 22 , 30 ]. In a previous study by our Institution, we noticed that miRNA 483-3p displayed a differential expression in HCC with peculiar vascular modifications characterizing advanced HCC [ 31 ]. Our current results showed that miR-483-3p is up-regulated in the non-recurrent group of patients and downregulated in the recurrence group, thus acting as a tumor-suppressor, at least in HCC.…”