Wilms’ tumour 1 gene expression is increased in hepatocellular carcinoma and associated with poor prognosis Toshiki Sera a , Yoichi Hiasa a , Toshie Mashiba a , Yoshio Tokumoto a , Masashi Hirooka a , Ichiro Konishi a , Bunzo Matsuura a , Kojiro Michitaka a , Keiko Udaka b , Morikazu Onji a, * a Department of Gastroenterologyand Metabology, Ehime University Graduate School of Medicine, Sitsukawa, Toon, Ehime 791-0295, Japan b Department of Immunology, Kochi Medical School, Kohasu, Oko, Nankoku, Kochi 783-8505, Japan ARTICLE INFO Article history: Received 31 October 2007 Received in revised form 21 December 2007 Accepted 7 January 2008 Available online 5 February 2008 Keywords: Wilms’ tumour 1 gene Hepatocellular carcinoma Oncogenic potential Prognosis ABSTRACT Background/aims: Wilms’ tumour 1 gene (WT1) was originally isolated as a tumour-suppres- sor gene. We investigated the expression of WT1 in hepatocellular carcinoma (HCC; T) and in non-cancerous hepatic tissues (non-tumour: NT) from patients with chronic liver diseases, and then examined the role of WT1 in the carcinogenesis or prognosis of HCC. Methods: The expression of WT1 in T and NT from 50 patients with HCC was investigated using Western blotting, immunohistochemistry and real-time reverse transcriptase- polymerase chain reaction (RT-PCR). We also examined whether WT1 expression was related to clinicopathological factors in individual patients in addition to prognostic factors in 50 patients with HCC and in 26 without HCC. Results: Western blotting and immunohistochemical staining showed that WT1 was over- expressed in T compared with NT (P < 0.001) and real-time RT-PCR showed that WT1 mRNA expression was similarly increased. Overexpressed WT1 in HCC was significantly associ- ated with T factors at the TNM stage, and short doubling time of HCC. Univariate and mul- tivariate analyses revealed that WT1 overexpression was an independent prognostic factor for HCC. The disease-free survival period in patients with overexpressed WT1 in NT tissues was significantly reduced. Conclusion: The expression of WT1 is increased more in HCC than in non-tumour tissues. Moreover, overexpressed WT1 was associated with tumour growth, and resulted in a wors- ening prognosis of HCC. Our findings from NT tissues revealed that WT1 overexpression might contribute to oncogenic potential. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Wilms’ tumour 1 gene (WT1) that was originally associated with Wilms’ tumour 1 is located at chromosome band 11p13 and encodes a transcription factor with four DNA-binding zinc fingers at the C terminus. 2 The gene regulates the tran- scription of several genes encoding growth factors and growth factor receptors, PDGF-A chain, IGF-II and IGF-IR by citing a few 3–5 as well as other genes (c-myc, bcl-2). 6 In normal human tissue, WT1 expression is restricted to the kidney, tes- tis, ovary, spleen, haematopoietic precursors and mesothelial cell lining of visceral organs. 6 The multifunctional roles of WT1 include activation or repression of transcription, nuclear transcription or RNA metabolism and translational regulation 0959-8049/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2008.01.008 * Corresponding author: Tel.: +81 89 960 5308; fax: +81 89 960 5310. E-mail address: onjimori@m.ehime-u.ac.jp (M. Onji). EUROPEAN JOURNAL OF CANCER 44 (2008) 600 – 608 available at www.sciencedirect.com journal homepage: www.ejconline.com