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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 7/2011

01-07-2011 | Translational Research and Biomarkers

Importin-α1 as a Novel Prognostic Target for Hepatocellular Carcinoma

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

Published in: Annals of Surgical Oncology | Issue 7/2011

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Abstract

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 importin-α1 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-α1 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-α1 as the only independent predictor of early recurrence after HCC resection (odds ratio = 5.291, P = 0.0191).

Conclusions

Because importin-α1 might be closely associated with HCC progression, further analysis should be pursued to evaluate it as a novel prognostic target.
Appendix
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Metadata
Title
Importin-α1 as a Novel Prognostic Target for Hepatocellular Carcinoma
Authors
Kenichiro Yoshitake, MD
Shinji Tanaka, MD, PhD, FACS
Kaoru Mogushi, PhD
Arihiro Aihara, MD, PhD
Ayano Murakata, MD
Satoshi Matsumura, MD
Yusuke Mitsunori, MD
Mahmut Yasen, MD, PhD
Daisuke Ban, MD, PhD
Norio Noguchi, MD, PhD
Takumi Irie, MD, PhD
Atsushi Kudo, MD, PhD
Noriaki Nakamura, MD, PhD
Hiroshi Tanaka, PhD
Shigeki Arii, MD, PhD
Publication date
01-07-2011
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 7/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-1569-7

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