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Importin-α1 as a Novel Prognostic Target for Hepatocellular Carcinoma

  • Translational Research and Biomarkers
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Annals of Surgical Oncology Aims and scope Submit manuscript

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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.

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Acknowledgment

This work was supported by a Grant-in Aid for Scientific Research and Health Labor Sciences Research Grant, Japan. We thank Ayumi Shioya for her technical assistance.

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Authors and Affiliations

  1. Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

    Kenichiro Yoshitake MD, Shinji Tanaka MD, PhD, FACS, 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 & Shigeki Arii MD, PhD

  2. Information Center for Medical Sciences, Tokyo Medical and Dental University, Tokyo, Japan

    Kaoru Mogushi PhD & Hiroshi Tanaka PhD

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  1. Kenichiro Yoshitake MD
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Corresponding author

Correspondence to Shinji Tanaka MD, PhD, FACS.

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Yoshitake, K., Tanaka, S., Mogushi, K. et al. Importin-α1 as a Novel Prognostic Target for Hepatocellular Carcinoma. Ann Surg Oncol 18, 2093–2103 (2011). https://doi.org/10.1245/s10434-011-1569-7

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  • DOI: https://doi.org/10.1245/s10434-011-1569-7

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