Genomic aberrations in hepatocellular carcinoma related to osteopontin expression detected by array-CGH.
OBJECTIVE
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.
Wu
Jin-Cai
JC
Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Sciences, Fudan University, 180 Feng Lin Road, 200032, Shanghai, People's Republic of China.
Sun
Bing-Sheng
BS
Ren
Ning
N
Ye
Qing-Hai
QH
Qin
Lun-Xiu
LX
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D055028:Comparative Genomic Hybridization; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism
D053495:Osteopontin