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 |
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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 |
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Affiliation: | 1.Department of Surgery,Chang Gung Memorial Hospital,Taoyuan,Taiwan;2.Graduate Institute of Clinical Medical Sciences,Chang Gung University,Taoyuan,Taiwan;3.Department of Biotechnology,Ming Chuan University,Taoyuan,Taiwan;4.Genomic Medicine Research Core Laboratory,Chang Gung Memorial Hospital,Taoyuan,Taiwan;5.Department of Pathology,Taipei Medical University Hospital,Taipei,Taiwan;6.Department of Pathology, Chang Gung Memorial Hospital,Chang Gung University,Taoyuan,Taiwan |
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Abstract: | BackgroundEarly 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.MethodsWe 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.ConclusionsElevation of both OPN and GPC3 may act as an adverse indicator for HBV-related small HCC patients after curative resection. |
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