Aurora kinase B is a predictive factor for the aggressive recurrence of hepatocellular carcinoma after curative hepatectomy.
BACKGROUND
Patterns of cancer recurrence hold the key to prognosis after curative resection. This retrospective study aimed to identify a predictor and therapeutic candidate for aggressive recurrence of hepatocellular carcinoma (HCC).


METHODS
Primary HCC tissues from 107 patients who had curative resection were analysed. Genome-wide gene expression profiles were investigated using a microarray technique, and clustering analysis was carried out based on the first diagnosis of recurrence according to the Milan criteria. Immunohistochemical expression and array-based comparative genomic hybridization (array-CGH) were also assessed.


RESULTS
Microarray analysis revealed overexpression of Aurora kinase B, a chromosome passenger protein kinase, as the most significant predictor of the aggressive recurrence of HCC. Aurora kinase B protein expression was significantly associated with aggressive recurrence (P < 0.001) and prognosis (P < 0.001). Multivariable analysis identified Aurora kinase B as the only independent predictor of aggressive recurrence of HCC (P = 0.031). Array-CGH analysis showed that genomic instability was closely related to Aurora kinase B expression (P = 0.011).


CONCLUSIONS
Aurora kinase B is an effective predictor of aggressive HCC recurrence, in relation to the genomic instability. It might be worth considering as a molecular target for the adjuvant therapy of HCC.
Tanaka
S
S
Information Centre for Medical Sciences, Tokyo Medical and Dental University, Tokyo, Japan. shinji.msrg@tmd.ac.jp
Arii
S
S
Yasen
M
M
Mogushi
K
K
Su
N T
NT
Zhao
C
C
Imoto
I
I
Eishi
Y
Y
Inazawa
J
J
Miki
Y
Y
Tanaka
H
H
D064107:Aurora Kinase B; D064127:Aurora Kinases; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D018572:Disease-Free Survival; D015870:Gene Expression; D042822:Genomic Instability; D006498:Hepatectomy / Q000401:mortality*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000032:analysis; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases