title: 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.
authors: Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei.
authors: Shu-Hsiang
authors: SH
authors: Liu
authors: Chiao-Ying
authors: CY
authors: Lin
authors: Shian-Yang
authors: SY
authors: Peng
authors: Yung-Ming
authors: YM
authors: Jeng
authors: Hung-Wei
authors: HW
authors: Pan
authors: Po-Lin
authors: PL
authors: Lai
authors: Chao-Lien
authors: CL
authors: Liu
authors: Hey-Chi
authors: HC
authors: Hsu
mesh_terms: D000328:Adult; D017302:Annexins / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D003001:Cloning, Molecular; D015536:Down-Regulation; D005333:Fetus / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D019043:Vascular Neoplasms / Q000556:secondary
chemical_list: D017302:Annexins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53