Published in:
01-04-2010 | Original Paper
Genomic aberrations in hepatocellular carcinoma related to osteopontin expression detected by array-CGH
Published in: Journal of Cancer Research and Clinical Oncology | Issue 4/2010
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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.