Aurora kinase B is a predictive factor for the aggressive recurrence of hepatocellular carcinoma after curative hepatectomy

Author:

Tanaka S12,Arii S2,Yasen M12,Mogushi K1,Su N T3,Zhao C4,Imoto I4,Eishi Y5,Inazawa J4,Miki Y3,Tanaka H1

Affiliation:

1. Information Centre for Medical Sciences, Tokyo Medical and Dental University, Tokyo, Japan

2. Department of Hepato-biliary-pancreatic Surgery, Graduate School of Medicine, Tokyo, Japan

3. Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

4. Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

5. Department of Pathology, Graduate School of Medicine, Tokyo, Japan

Abstract

Abstract 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). Conclusion 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.

Funder

Special Coordination Funds for Promoting Science and Technology

Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan

Japan Cancer Society Incitement Award

Japan Society for the Promotion of Science Prize

Publisher

Oxford University Press (OUP)

Subject

Surgery

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