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

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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26 Citations (Scopus)

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.

Original languageEnglish
JournalAnnals of Surgical Oncology
Volume19
Issue numberSUPPL. 3
DOIs
Publication statusPublished - Jul 1 2012

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Glypicans
Osteopontin
Hepatitis B
Hepatocellular Carcinoma
Hepatitis B virus
Recurrence
Neoplasms
Disease-Free Survival
Oligonucleotide Array Sequence Analysis
Survival
Real-Time Polymerase Chain Reaction
Immunohistochemistry
Genes

ASJC Scopus subject areas

  • Surgery
  • Oncology

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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. / Yu, Ming Chin; Lee, Yun Shien; Lin, Sey-En; Wu, Hsiang Yao; Chen, Tse Ching; Lee, Wei Chen; Chen, Miin Fu; Tsai, Chi Neu.

In: Annals of Surgical Oncology, Vol. 19, No. SUPPL. 3, 01.07.2012.

Research output: Contribution to journalArticle

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title = "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.",
author = "Yu, {Ming Chin} and Lee, {Yun Shien} and Sey-En Lin and Wu, {Hsiang Yao} and Chen, {Tse Ching} and Lee, {Wei Chen} and Chen, {Miin Fu} and Tsai, {Chi Neu}",
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T1 - 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

AU - Yu, Ming Chin

AU - Lee, Yun Shien

AU - Lin, Sey-En

AU - Wu, Hsiang Yao

AU - Chen, Tse Ching

AU - Lee, Wei Chen

AU - Chen, Miin Fu

AU - Tsai, Chi Neu

PY - 2012/7/1

Y1 - 2012/7/1

N2 - 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.

AB - 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.

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