TY - JOUR
T1 - Importin-α1 as a novel prognostic target for hepatocellular carcinoma
AU - Yoshitake, Kenichiro
AU - Tanaka, Shinji
AU - Mogushi, Kaoru
AU - Aihara, Arihiro
AU - Murakata, Ayano
AU - Matsumura, Satoshi
AU - Mitsunori, Yusuke
AU - Yasen, Mahmut
AU - Ban, Daisuke
AU - Noguchi, Norio
AU - Irie, Takumi
AU - Kudo, Atsushi
AU - Nakamura, Noriaki
AU - Tanaka, Hiroshi
AU - Arii, Shigeki
N1 - Funding Information:
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.
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
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U2 - 10.1245/s10434-011-1569-7
DO - 10.1245/s10434-011-1569-7
M3 - Article
C2 - 21286940
AN - SCOPUS:80051551587
VL - 18
SP - 2093
EP - 2103
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
SN - 1068-9265
IS - 7
ER -
