Down-Regulation of Annexin A10 in Hepatocellular Carcinoma Is Associated with Vascular Invasion, Early Recurrence, and Poor Prognosis in Synergy with p53 Mutation

Abstract

Annexins (ANXs) are a large group of calcium-binding proteins participating in diverse important biological processes. ANXA10 is the least expressed new member of unknown function. We showed that ANXA10 mRNA was expressed in adult liver and hepatocellular carcinoma (HCC), but not in multiple adult and fetal tissues, cholangiocarcinoma, and several other common carcinomas. Of 182 unifocal primary HCCs, ANXA10 mRNA was dramatically reduced in 121 (66%), and the down-regulation correlated with p53 mutation (P ‫؍‬ 0.024), early intrahepatic tumor recurrence (P ‫؍‬ 0.0007), and lower 4-year survival (P ‫؍‬ 0.0014). Down-regulation of ANXA10 was twofold more frequent in large than small HCCs (P ‫؍‬ 0.0012), in grade II to III than grade I HCC (P < 0.00001), and in stage IIIA to IV than stage I to II HCC (P < 0.00001). Moreover, ANXA10 down-regulation and p53 mutation acted synergistically toward high-grade (P < 0.00001), high-stage HCC (P < 0.00001), and poorer prognosis (P ‫؍‬ 0.0025). Our results indicate that the expression of the tissue-and tumor-restricted ANXA10 is a marker of liver cell differentiation and growth arrest, and its down-regulation associated with malignant phenotype of hepatocytes, vascular invasion, and progression of HCC, leading to poor prognosis. Thus, ANXA10 might serve as a new potential target of gene therapy for HCC.

Overexpression of NDRG1 is an indicator of poor prognosis in hepatocellular carcinoma

“…25,26 Many factors modulate the propensity of malignant tumors for vascular invasion, of which altered cell-cell and cell-matrix interactions play a critical role. [27][28][29] Additionally, factors involved in angiogenesis (eg vascular endothelial growth factor receptor), 25 cell differentiation and growth arrest (eg annexin A10), 30 tumor …”

Decreased expression of Annexin A10 in gastric cancer and its overexpression in tumor cell growth suppression

“…Chromosome 4q is one of the most common regions associated with a high frequency of allelic loss in hepatocellular carcinoma (32)(33)(34)(35). However, despite the accumulating evidence supporting aberrant expression of ANXA10 and a high frequency of allelic loss of the ANXA10 gene, in specific types of cancer (21,36), there is no information on its biological activity in various types of cancer, especially in gastric carcinoma. ANXA10 expression has been shown to be reduced in gastric carcinoma based on the findings of previous studies.…”

“…The activity of these proteins are mediated by Ca 2+ dependent signal transduction pathways also involved in the regulation of the cell cycle, growth, vesicle trafficking, and apoptosis (14)(15)(16)(17)(18)(19) (20). The downregulation of the ANXA10 protein, was first identified in higher vertebrates, and has been correlated with the presence of a p53 mutation and poor prognosis in patients with hepatocellular carcinoma (21). Recently, ANXA10 expression was found to be reduced in mucinous adenocarcinoma, and low ANXA10 expression was also found to be associated with a poor prognosis (13).…”

Expression and significance of transient receptor potential cation channel V5 in articular cartilage cells under exercise loads

“…TRPV5 is co-expressed with the majority of calcium-binding proteins in tissues, among which Annexins (ANXs) are closely associated with cell growth, differentiation and infiltration. Annexin A10 expression is a sign of histocyte differentiation and growth arrest, which is closely associated with the malignant phenotype of histocytes, vascular invasion and tumor progression (18). Annexin A2 downregulation can block TRPV5-mediated current.…”