Elsevier

Surgery

Volume 149, Issue 6, June 2011, Pages 783-791
Surgery

Original Communication
Specific expression of osteopontin and S100A6 in hepatocellular carcinoma

https://doi.org/10.1016/j.surg.2010.12.007Get rights and content

Background

Our aim was to identify differential expression of genes in hepatocellular carcinoma (HCC) with the ultimate goal of discovering novel diagnostic and therapeutic targets.

Methods

We examined differences in gene expression between HCC and noncancerous liver tissue using a cDNA array with probes for 15,843 genes/clones. Two genes, osteopontin (OPN) and S100A6, were found to be >10-fold differentially expressed, and were selected for further immunohistochemical staining in 51 HCC and 10 nonmalignant liver specimens. The relation between OPN and S100A6 alterations and various clinicopathologic parameters was also evaluated.

Results

We found a total of 219 genes that were differentially expressed >3-fold. Of these, 109 were upregulated and 110 downregulated. Within this group, 123 genes, including 59 upregulated and 64 downregulated, had been identified previously. These known genes were mainly involved in cell migration, cytoskeleton dynamics, the signaling pathway and cell cycle, and metabolism. OPN expression and S100A6 expression were seen in 26 of 51 (51.0 %) and 16 of 51 (31.4 %) HCC samples, respectively. More importantly, proteins coded by these genes were not found in any noncancerous liver specimen by immunohistochemical analysis. Expression of these genes correlated with poor differentiation (OPN: P = .013; S100A6: P = .008).

Conclusion

OPN, a secreted phosphoprotein that has been increasingly implicated in the progression and metastasis of cancer, and S100A6, a member of the S100 protein family that can perform cell proliferation, differentiation, migration, and cytoskeletal dynamics, may be promising diagnostic markers and therapeutic targets for HCC. In addition, the results encourage future studies involving the roles of these proteins in the development and progression of this cancer.

Section snippets

Patients and specimens

Prospective tissue collection was obtained with institutional approval and informed consent. For microarray analysis, HCC as well as noncancerous tissue were excised during partial hepatectomy in a patient with recurrent HCC. Tissues were snap-frozen in liquid nitrogen and stored at −80°C before RNA extraction.

For retrospective immunohistochemical studies, 51 specimens of HCC were retrieved from the pathology archives ranging from 1996 to 2004 of China-Japan Friendship Hospital in China. Of

Differential gene expression in HCC compared with normal liver tissue

The cDNA array sequences represented 15,843 known genes and ESTs. Quality control of the cDNA array was evaluated by coefficient of variation and scatter plots of double spots. The coefficients of variation of double spots of HCC and noncancerous liver were 16.3% and 17.5%, respectively; the square of Pearson correlation coefficiencies (r2) of scatter plots of double spots were .9858 and .9874, respectively (Fig 1). These demonstrated that the cDNA array system was highly reliable and

Discussion

Combining cDNA array and immunohistochemical staining as screens has proven highly successful in identifying dissecting pathways pivotal to many biologic processes, including cancer development and progression. Using subtraction hybridization, a large number of genes can be screened for upregulation in diseased conditions.8, 9, 10, 11, 12, 13, 14 Immunohistochemical staining can then be assayed for correlation between gene expression and protein expression, and allows analysis of larger numbers

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