Gene-expression phenotypes for vascular invasiveness of hepatocellular carcinomas

Shinji Tanaka, Kaoru Mogushi, Mahmut Yasen, Norio Noguchi, Atsushi Kudo, Noriaki Nakamura, Koji Ito, Yoshio Miki, Johji Inazawa, Hiroshi Tanaka, Shigeki Arii

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Background: Gross vascular invasion is a well-established prognostic indicator in hepatocellular carcinoma (HCC), but the biological significance of microscopic invasion remains unclear. Methods: Curatively resected primary HCCs were classified retrospectively into 3 groups: HCCs without vascular invasion (V0), HCCs with microvascular invasion (V1), and HCCs with macrovascular invasion (V2). Microarray profiling of patients with V0, V1, and V2 using Jonckheere-Terpstra (JT) tests and Wilcoxon rank sum tests was performed. Results: Distinct patterns of gene expression were demonstrated between V0 and V2 groups; less (L) and highly (H) invasive phenotypes, respectively. It is noteworthy that 2 dendrograms by the hierarchical clustering provided exactly the same assignment results for V1 cases that were thus separated into L and H gene-expression phenotypes. Marked differences were found in overall (P < .001) and tumor-free survival (P < .001) between L and H gene-expression phenotypes. Multivariate analyses indicated that the phenotypes of the patterns of gene expression, rather than the clinicopathologic markers of vascular invasion, were independent predictors of tumor recurrence (P = .031). Using the gene-expression patterns identified by both JT and Wilcoxon rank sum test analyses, other V1 cases validated these differences in tumor-free survivals between gene-expression phenotypes within the group (P = .039). Conclusion: Gene profiling suggested that microvascular invasiveness consisted of a classable mixture of 2 distinct phenotypes. Thus, gene-array analyses may have clinical benefit, because they may in fact be more predictive than other clinical factors.

Original languageEnglish
Pages (from-to)405-414
Number of pages10
Issue number3
Publication statusPublished - 2010 Mar
Externally publishedYes

ASJC Scopus subject areas

  • Surgery


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