Down-regulation of annexin A10 in hepatocellular carcinoma is associated with vascular invasion, early recurrence, and poor prognosis in synergy with p53 mutation.
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.
Liu
Shu-Hsiang
SH
Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei.
Lin
Chiao-Ying
CY
Peng
Shian-Yang
SY
Jeng
Yung-Ming
YM
Pan
Hung-Wei
HW
Lai
Po-Lin
PL
Liu
Chao-Lien
CL
Hsu
Hey-Chi
HC
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
D017302:Annexins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53