Recurrence-associated pathways in hepatitis B virus-positive hepatocellular carcinoma

Bu Yeo Kim, Wook D. Choi, Rang S. Woo, Eun Ran Park, Je Geun Lee, Su Hyeon Kim, Imhoi Koo, Sun Hoo Park, Ju C. Han, Bum S. Kim, Il Y. Yeom, Suk Jin Yang, Ami Yu, Won J. Lee, June J. Jang, Myung Haing Cho, Kyung W. Jeon, Nyun Y. Park, Kyung Suk Suh, Kee Ho Lee

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Abstract

Background: Despite the recent identification of several prognostic gene signatures, the lack of common genes among experimental cohorts has posed a considerable challenge in uncovering the molecular basis underlying hepatocellular carcinoma (HCC) recurrence for application in clinical purposes. To overcome the limitations of individual gene-based analysis, we applied a pathway-based approach for analysis of HCC recurrence. Results: By implementing a permutation-based semi-supervised principal component analysis algorithm using the optimal principal component, we selected sixty-four pathways associated with hepatitis B virus (HBV)-positive HCC recurrence (p < 0.01), from our microarray dataset composed of 142 HBV-positive HCCs. In relation to the public HBV- and public hepatitis C virus (HCV)-positive HCC datasets, we detected 46 (71.9%) and 18 (28.1%) common recurrence-associated pathways, respectively. However, overlap of recurrence-associated genes between datasets was rare, further supporting the utility of the pathway-based approach for recurrence analysis between different HCC datasets. Non-supervised clustering of the 64 recurrence-associated pathways facilitated the classification of HCC patients into high- and low-risk subgroups, based on risk of recurrence (p < 0.0001). The pathways identified were additionally successfully applied to discriminate subgroups depending on recurrence risk within the public HCC datasets. Through multivariate analysis, these recurrence-associated pathways were identified as an independent prognostic factor (p < 0.0001) along with tumor number, tumor size and Edmondson's grade. Moreover, the pathway-based approach had a clinical advantage in terms of discriminating the high-risk subgroup (N = 12) among patients (N = 26) with small HCC (<3 cm). Conclusions: Using pathway-based analysis, we successfully identified the pathways involved in recurrence of HBV-positive HCC that may be effectively used as prognostic markers.

Original languageEnglish (US)
Article number279
JournalBMC genomics
Volume16
Issue number1
DOIs
StatePublished - Apr 10 2015

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All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Genetics

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Kim, B. Y., Choi, W. D., Woo, R. S., Park, E. R., Lee, J. G., Kim, S. H., Koo, I., Park, S. H., Han, J. C., Kim, B. S., Yeom, I. Y., Yang, S. J., Yu, A., Lee, W. J., Jang, J. J., Cho, M. H., Jeon, K. W., Park, N. Y., Suh, K. S., & Lee, K. H. (2015). Recurrence-associated pathways in hepatitis B virus-positive hepatocellular carcinoma. BMC genomics, 16(1), [279]. https://doi.org/10.1186/s12864-015-1472-x