Importin-α1 as a novel prognostic target for hepatocellular carcinoma

Kenichiro Yoshitake, Shinji Tanaka, Kaoru Mogushi, Arihiro Aihara, Ayano Murakata, Satoshi Matsumura, Yusuke Mitsunori, Mahmut Yasen, Daisuke Ban, Norio Noguchi, Takumi Irie, Atsushi Kudo, Noriaki Nakamura, Hiroshi Tanaka, Shigeki Arii

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


Background. Perturbations in the nuclear microenvironment, including transport systems, play a critical role in malignant progression, but the nuclear import abnormalities remain unclear in hepatocarcinogenesis. We analyzed the role of importin in hepatocellular carcinoma (HCC). Methods. Gene expression profiling of the importin family was performed in HCC tissues. The significance of importin protein expression was analyzed in vitro as well as clinicopathologically. Results. According to the microarray profiles, the importina1 was dominantly overexpressed in HCC tissues as compared to the adjacent noncancerous tissues. By means of human HCC cell lines, a knockdown of importin-α1 by its siRNA greatly reduced cellular proliferation by 15.2-26.6% (P<0.005). Immunohistochemical analysis on tissue samples demonstrated cancer-specific overexpression in 36.3% of HCCs. The overexpression of importin-α1 was correlated statistically with high levels of alfa-fetoprotein (P = 0.0017), the tumor number (P = 0.0116), histological dedifferentiation (P = 0.0054), tumor morphology (P = 0.0433), portal vein invasion (P = 0.0007), hepatic vein invasion (P = 0.0081), Fc (P = 0.0367), Fc-inf (P = 0.0122), and the tumor, node, metastasis stage (P = 0.0026); this resulted in a significantly poorer prognosis in both overall survival (P = 0.0164) and recurrence-free survival (P = 0.0101). Multivariate analysis of recurrence-free survival revealed importin-a1 expression to be a statistically significant factor (P = 0.0361). In addition, early recurrence after curative resection was observed more frequently in the importin-α1-positive group as compared to the negative group (P = 0.0023). The multivariate analysis identified importin-a1 as the only independent predictor of early recurrence after HCC resection (odds ratio = 5.291, P = 0.0191). Conclusions. Because importin-a1 might be closely associated with HCC progression, further analysis should be pursued to evaluate it as a novel prognostic target.

Original languageEnglish
Pages (from-to)2093-2103
Number of pages11
JournalAnnals of Surgical Oncology
Issue number7
Publication statusPublished - 2011 Jul

ASJC Scopus subject areas

  • Surgery
  • Oncology


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