BERKELEY, CA (UroToday.com) - We previously demonstrated that Twist1 is involved in both drug resistance and tumor growth via YB-1 expression.[1] Moreover, p53 downregulates the transcriptional activity of Twist1 and YB-1, and, conversely, both Twist1 and YB-1 can rescue p53-mediated growth suppression in human cancer cells.[2] Furthermore, we reported that programmed cell-death protein 4 interacted with Twist1, downregulated YB-1 expression, and was involved in drug resistance to cisplatin and paclitaxel.[3] Recently, we reported that Twist1 regulates YB-1 expression and that both Twist1 and YB-1 promote malignant potentials in bladder cancer cell lines.[4]
In the current study, Twist1 and YB-1 expression were investigated in clinical bladder cancer samples, and the correlations between Twist1 and YB-1 expression, and between expression level and clinicopathologic parameters were explored.
Frozen samples from 75 patients with bladder cancer were analyzed by quantitative real-time PCR (qRT-PCR). Formalin-fixed and paraffin-embedded tissues from 53 patients with bladder cancer were examined by immunohistochemistry.
Twist1 transcript levels were positively correlated with YB-1 transcript levels (coefficient of correlation= 0.42, P < 0.001), tumor grade (low grade vs. high grade; P < 0.001), invasiveness (NMIBC vs. MIBC; P = 0.0018), and metastasis (meta- vs. meta+; P < 0.001). YB-1 transcript level was also correlated with grade (P = 0.029) and invasiveness (P = 0.006). By immunohistochemistry, Twist1 expression was also correlated with YB-1 expression (P < 0.001). Further, both Twist1 and YB-1 expression was positively correlated with invasiveness (P = 0.007 and P = 0.002, respectively). Patients with high Twist1 expression and high YB-1 expression had lower overall survival rates, compared with patients with low expression (log-rank test, P = 0.040 and P < 0.001, respectively).
As reported previously, both Twist1 and YB-1 were implicated in cancer cell proliferation.[1] Twist1 is known to regulate the invasive and metastatic characteristics of cancer cells.[5] YB-1 has also recently been shown to regulate cancer cell invasion.[6, 7] In this study, both Twist1 and YB-1 gene expression level, as well as expression detected by immunostaining, were correlated with tumor grade, tumor stage, or metastasis status, suggesting that Twist1 and YB-1 play a role in bladder cancer growth and invasion. The clarification of their roles in this study may pave the way for new effective treatment. The expression of Twist1 and YB-1 as revealed by immunohistochemistry could predict overall survival, although only YB-1 was an independent prognostic factor when multivariate analysis was performed. These findings suggest that YB-1 immunostaining combined with conventional clinicopathological parameters may improve the predictive ability of disease prognosis.
References:
- Shiota M, Izumi H, Onitsuka T, Miyamoto N, Kashiwagi E, Kidani A, Yokomizo A, Naito S, Kohno K. Twist promotes tumor cell growth through YB-1 expression. Cancer Res. 2008; 68:98-105.
- Shiota M, Izumi H, Onitsuka T, Miyamoto N, Kashiwagi E, Kidani A, Hirano G, Takahashi M, Naito S, Kohno K. Twist and p53 reciprocally regulate target genes via direct interaction. Oncogene 2008; 27:5543-53.
- Shiota M, Izumi H, Tanimoto A, Takahashi M, Miyamoto N, Kashiwagi E, Kidani A, Hirano G, Masubuchi D, Fukunaka Y, Yasuniwa Y, Naito S, Nishizawa S, Sasaguri Y, Kohno K. Programmed cell death protein 4 down-regulates Y-box binding protein-1 expression via a direct interaction with Twist1 to suppress cancer cell growth. Cancer Res. 2009; 69:3148-56.
- Shiota M, Yokomizo A, Itsumi M, Uchiumi T, Tada Y, Song Y, Kashiwagi E, Masubuchi D, Naito S. Twist1 and Y-box-binding protein-1 promote malignant potential in bladder cancer cells. BJU Int. 2011; 108:E142-9.
- Yang J, Mani SA, Weinberg RA. Exploring a new twist on tumor metastasis. Cancer Res. 2006; 66:4549-52.
- Evdokimova V, Tognon C, Ng T, Ruzanov P, Melnyk N, Fink D, Sorokin A, Ovchinnikov LP, Davicioni E, Triche TJ, Sorensen PH. Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition. Cancer.Cell. 2009; 15:402-15.
- Astanehe A, Finkbeiner MR, Hojabrpour P, To K, Fotovati A, Shadeo A, Stratford AL, Lam WL, Berquin IM, Duronio V, Dunn SE. The transcriptional induction of PIK3CA in tumor cells is dependent on the oncoprotein Y-box binding protein-1. Oncogene 2009; 28:2406-18.
Written by:
YooHyun Song, PhD, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuokasi Higasiku Maidasi 3-1-1, Fukuoka 812-8582, Japan
Twist1 and Y-box-binding protein-1 are potential prognostic factors in bladder cancer - Abstract
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