Recurrence and poor prognosis following resection of small hepatitis B-related hepatocellular carcinoma lesions are associated with aberrant tumor expression profiles of glypican 3 and osteopontin.

Abstract

BACKGROUND:

Early detection and following appropriate treatments of hepatocellular carcinoma (HCC) is still the gold standard for favored outcome of HCC patients; nevertheless, a small portion of hepatitis B virus (HBV)-related small HCC (<5 cm) patients got poor prognosis. Furthermore, the study for small HBV-HCC was limited. Therefore, the aim of this study was to explore the potential genetic signature for HBV-related small HCC as novel prognostic factors.

METHODS:

We examined expression profiles of HBV-related small HCC using an Affymetrix U133A GeneChip, evaluated differential gene expression by quantitative real-time polymerase chain reaction (qRT-PCR), and finally validated these expression patterns by immunohistochemistry (IHC).

RESULTS:

A total of 57 genes were differentially expressed between tumor and normal parts (n = 20 pairs) using Affymetrix U133A chip, and 16 genes were further evaluated by qRT-PCR. The result was compatible with the finding of oligonucleotide microarray (Pearson's correlation, r = 0.87). Furthermore, the expression pattern in HCC tissue by IHC in another group of small HBV-HCC (n = 100) showed overexpression of either osteopontin (OPN) or glypican 3 (GPC3) is an independent prognostic factor for disease-free survival (DFS) in HBV-positive small HCC (P < 0.01 and 0.03, respectively). Long-term DFS and overall survival (OS) for small HBV-HCC patients with high risk (both elevated GPC3(+)/OPN(+)) were DFS 0%, OS 0%, respectively; on the other hand, DFS and OS in patients with moderate (only 1 gene elevated) or low (OPN(-)/GPC3(-)) risk were 35.0 and 46.5%, respectively.

CONCLUSIONS:

Elevation of both OPN and GPC3 may act as an adverse indicator for HBV-related small HCC patients after curative resection.

• Authors: Ming-Chin Yu, Yun-Shien Lee, Sey-En Lin, Hsiang-Yao Wu, Tse-Ching Chen, Wei-Chen Lee, Miin-Fu Chen, Chi-Neu Tsai
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 19 Suppl 3 Pg. S455-63 (Jul 2012) ISSN: 1534-4681 [Electronic] United States
• PMID: 21822558 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glypicans
• Osteopontin

Topics

• Carcinoma, Hepatocellular (genetics, metabolism, virology)
• Cell Adhesion (genetics)
• Cell Proliferation
• Chemotaxis (genetics)
• Disease-Free Survival
• Down-Regulation
• Gene Expression Profiling
• Genes, Neoplasm
• Glypicans (genetics, metabolism)
• Hepatitis B virus
• Hepatitis B, Chronic (complications)
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Liver Neoplasms (genetics, metabolism, virology)
• Neoplasm Recurrence, Local (genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• Osteopontin (genetics, metabolism)
• Proportional Hazards Models
• Up-Regulation