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

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 realtime 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.