Genomic aberrations in hepatocellular carcinoma related to osteopontin expression detected by array-CGH.

Abstract:

PURPOSE:We have demonstrated that overexpression of osteopontin (OPN) could contribute to metastasis in hepatocellular carcinoma (HCC), and that OPN-positive cancer cells are often localized in the periphery of cancer nodules adjacent to stromal cells. This study was to identify the difference of intratumor genomic aberrations between OPN-positive and OPN-negative HCC cells. METHODS:Immunohistochemical staining for OPN was performed in both archival and fresh HCC tumor tissues. Seven cases of OPN-positive HCC were chosen for laser capture microdissection. The OPN-positive and OPN-negative cancer cells were captured separately from serial frozen sections. Genomic DNA was extracted and quantified. Microarray-based comparative genomic hybridization (array-CGH) was used to achieve high-resolution analysis of whole-genome-wide aberrations. RESULTS:The OPN expression level in HCC tissues was significantly associated with vascular or bile duct invasion (P = 0.003), Edmondson's grade (P = 0.047), and intrahepatic spreading (P = 0.011). When compared with the OPN-negative cancer cells, much more amplifications of chromosomal regions, including 4q13.1-q13.3, 4q21.23-q22.1, and 13q32.1-q32.3, were found in OPN-positive HCC cells. Some candidate tumor-related genes, such as SMR3B, MUC7, EPHA5, SPP1, and CLDN10 were detected with over 1.5-fold amplification. CONCLUSIONS:There is a significant intratumor genomic heterogeneity between the OPN-positive and negative HCC cells, and OPN-positive HCC cells play a more important role in the development of HCC malignancy than their OPN-negative counterparts.

authors

Wu JC,Sun BS,Ren N,Ye QH,Qin LX

doi

10.1007/s00432-009-0695-0

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

595-601

issue

4

eissn

0171-5216

issn

1432-1335

journal_volume

136

pub_type

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