Significance of DEK overexpression for the prognostic evaluation of non-small cell lung carcinoma

Liu,Xin; Qi,Dongdong; Qi,Jujie; Mao,Zeshu; Li,Xiangdan; Zhang,Jinhui; Li,Jinzi; Gao,Wenbin

doi:10.3892/or.2015.4365

Significance of DEK overexpression for the prognostic evaluation of non-small cell lung carcinoma

Authors:
- Xin Liu
- Dongdong Qi
- Jujie Qi
- Zeshu Mao
- Xiangdan Li
- Jinhui Zhang
- Jinzi Li
- Wenbin Gao
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Affiliations: Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong, Liaoning 118000, P.R. China, Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116000, P.R. China, Traditional Chinese Medical Hospital of Anqiu City, Anqiu, Shandong 262100, P.R. China, Department of Pediatrics, Yanbian University Hospital, Yanji, Jilin 133002, P.R. China
Published online on: October 30, 2015 https://doi.org/10.3892/or.2015.4365
Pages: 155-162

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Abstract

In the present study, we explored the role of DEK expression for the prognostic evaluation of non-small cell lung carcinoma (NSCLC). DEK protein and mRNA expression levels were detected in NSCLC cells and fresh tissue samples of NSCLC paired with adjacent non-tumor tissues, respectively. NSCLC cases (n=196) meeting strict follow-up criteria were selected for immunohistochemical staining of DEK protein. Correlations between DEK expression and clinicopathological features of the NSCLC cases were evaluated using Chi-square tests. Survival rates were calculated using the Kaplan-Meier method, and the relationship between prognostic factors and patient overall survival was analyzed using Cox proportional hazard analysis. Based on the results, the levels of DEK protein and mRNA were significantly upregulated in 6 fresh tissue samples of NSCLC. Immunohistochemical analysis showed that the DEK expression rate was significantly higher in the NSCLC samples compared with either the adjacent non-tumor tissues or normal lung tissues. DEK expression was correlated with poor differentiation and late pathological stage of NSCLC. DEK expression was also correlated with low disease-free survival and overall survival rates. In the early-stage group, disease-free and overall survival rates of patients with DEK expression were significantly lower than those of patients without DEK expression. Further analysis using a Cox proportional hazard regression model revealed that DEK expression emerged as a significant independent hazard factor for the overall survival rate of patients with NSCLC. Consequently, DEK plays an important role in the progression of NSCLC. DEK may potentially be used as an independent biomarker for the prognostic evaluation of NSCLC.

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1	Jemal A, Siegel R, Ward E, Murray T, Xu J and Thun MJ: Cancer statistics, 2007. CA Cancer J Clin. 57:43–66. 2007. View Article : Google Scholar : PubMed/NCBI
2	Brambilla E, Travis WD, Colby TV, Corrin B and Shimosato Y: The new World Health Organization classification of lung tumours. Eur Respir J. 18:1059–1068. 2001. View Article : Google Scholar
3	Lee HW, Kim EH and Oh MH: Clinicopathologic implication of ezrin expression in non-small cell lung cancer. Korean J Pathol. 46:470–477. 2012. View Article : Google Scholar : PubMed/NCBI
4	von Lindern M, Fornerod M, van Baal S, Jaegle M, de Wit T, Buijs A and Grosveld G: The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA. Mol Cell Biol. 12:1687–1697. 1992. View Article : Google Scholar : PubMed/NCBI
5	Wise-Draper TM, Mintz-Cole RA, Morris TA, Simpson DS, Wikenheiser-Brokamp KA, Currier MA, Cripe TP, Grosveld GC and Wells SI: Overexpression of the cellular DEK protein promotes epithelial transformation in vitro and in vivo. Cancer Res. 69:1792–1799. 2009. View Article : Google Scholar : PubMed/NCBI
6	Privette Vinnedge LM, Ho SM, Wikenheiser-Brokamp KA and Wells SI: The DEK oncogene is a target of steroid hormone receptor signaling in breast cancer. PLoS One. 7:e469852012. View Article : Google Scholar : PubMed/NCBI
7	Cleary J, Sitwala KV, Khodadoust MS, Kwok RP, Mor-Vaknin N, Cebrat M, Cole PA and Markovitz DM: p300/CBP-associated factor drives DEK into interchromatin granule clusters. J Biol Chem. 280:31760–31767. 2005. View Article : Google Scholar : PubMed/NCBI
8	Khodadoust MS, Verhaegen M, Kappes F, Riveiro-Falkenbach E, Cigudosa JC, Kim DS, Chinnaiyan AM, Markovitz DM and Soengas MS: Melanoma proliferation and chemoresistance controlled by the DEK oncogene. Cancer Res. 69:6405–6413. 2009. View Article : Google Scholar : PubMed/NCBI
9	Privette Vinnedge LM, McClaine R, Wagh PK, Wikenheiser-Brokamp KA, Waltz SE and Wells SI: The human DEK oncogene stimulates β-catenin signaling, invasion and mammosphere formation in breast cancer. Oncogene. 30:2741–2752. 2011. View Article : Google Scholar : PubMed/NCBI
10	Hasiów-Jaroszewska B, Borodynko N and Pospieszny H: Infectious RNA transcripts derived from cloned cDNA of a pepino mosaic virus isolate. Arch Virol. 154:853–856. 2009. View Article : Google Scholar : PubMed/NCBI
11	Han S, Xuan Y, Liu S, Zhang M, Jin D, Jin R and Lin Z: Clinicopathological significance of DEK overexpression in serous ovarian tumors. Pathol Int. 59:443–447. 2009. View Article : Google Scholar : PubMed/NCBI
12	Wu Q, Li Z, Lin H, Han L, Liu S and Lin Z: DEK overexpression in uterine cervical cancers. Pathol Int. 58:378–382. 2008. View Article : Google Scholar : PubMed/NCBI
13	Lin L, Piao J, Gao W, Piao Y, Jin G, Ma Y, Li J and Lin Z: DEK over expression as an independent biomarker for poor prognosis in colorectal cancer. BMC Cancer. 13:3662013. View Article : Google Scholar : PubMed/NCBI
14	Liu S, Wang X, Sun F, Kong J, Li Z and Lin Z: DEK overexpression is correlated with the clinical features of breast cancer. Pathol Int. 62:176–181. 2012. View Article : Google Scholar : PubMed/NCBI
15	Wrona A and Jassem J: The new TNM classification in lung cancer. Pneumonol Alergol Pol. 78:407–417. 2010.In Polish.
16	Kappes F, Burger K, Baack M, Fackelmayer FO and Gruss C: Subcellular localization of the human proto-oncogene protein DEK. J Biol Chem. 276:26317–26323. 2001. View Article : Google Scholar : PubMed/NCBI
17	Kappes F, Scholten I, Richter N, Gruss C and Waldmann T: Functional domains of the ubiquitous chromatin protein DEK. Mol Cell Biol. 24:6000–6010. 2004. View Article : Google Scholar : PubMed/NCBI
18	Alexiadis V, Waldmann T, Andersen J, Mann M, Knippers R and Gruss C: The protein encoded by the proto-oncogene DEK changes the topology of chromatin and reduces the efficiency of DNA replication in a chromatin-specific manner. Genes Dev. 14:1308–1312. 2000.PubMed/NCBI
19	Campillos M, García MA, Valdivieso F and Vázquez J: Transcriptional activation by AP-2alpha is modulated by the oncogene DEK. Nucleic Acids Res. 31:1571–1575. 2003. View Article : Google Scholar : PubMed/NCBI
20	Soares LM, Zanier K, Mackereth C, Sattler M and Valcárcel J: Intron removal requires proofreading of U2AF/3′ splice site recognition by DEK. Science. 312:1961–1965. 2006. View Article : Google Scholar : PubMed/NCBI
21	Kavanaugh GM, Wise-Draper TM, Morreale RJ, Morrison MA, Gole B, Schwemberger S, Tichy ED, Lu L, Babcock GF, Wells JM, et al: The human DEK oncogene regulates DNA damage response signaling and repair. Nucleic Acids Res. 39:7465–7476. 2011. View Article : Google Scholar : PubMed/NCBI
22	Carro MS, Spiga FM, Quarto M, Di Ninni V, Volorio S, Alcalay M and Müller H: DEK Expression is controlled by E2F and deregulated in diverse tumor types. Cell Cycle. 5:1202–1207. 2006. View Article : Google Scholar : PubMed/NCBI
23	Casas S, Nagy B, Elonen E, Aventín A, Larramendy ML, Sierra J, Ruutu T and Knuutila S: Aberrant expression of HOXA9, DEK, CBL and CSF1R in acute myeloid leukemia. Leuk Lymphoma. 44:1935–1941. 2003. View Article : Google Scholar
24	Kroes RA, Jastrow A, McLone MG, Yamamoto H, Colley P, Kersey DS, Yong VW, Mkrdichian E, Cerullo L, Leestma J, et al: The identification of novel therapeutic targets for the treatment of malignant brain tumors. Cancer Lett. 156:191–198. 2000. View Article : Google Scholar : PubMed/NCBI
25	Kappes F, Khodadoust MS, Yu L, Kim DS, Fullen DR, Markovitz DM and Ma L: DEK expression in melanocytic lesions. Hum Pathol. 42:932–938. 2011. View Article : Google Scholar : PubMed/NCBI
26	Liu K, Feng T, Liu J, Zhong M and Zhang S: Silencing of the DEK gene induces apoptosis and senescence in CaSki cervical carcinoma cells via the up-regulation of NF-κB p65. Biosci Rep. 32:323–332. 2012. View Article : Google Scholar : PubMed/NCBI
27	Paderova J, Orlic-Milacic M, Yoshimoto M, da Cunha Santos G, Gallie B and Squire JA: Novel 6p rearrangements and recurrent translocation breakpoints in retinoblastoma cell lines identified by spectral karyotyping and mBAND analyses. Cancer Genet Cytogenet. 179:102–111. 2007. View Article : Google Scholar : PubMed/NCBI
28	Privette Vinnedge LM, Kappes F, Nassar N and Wells SI: Stacking the DEK: From chromatin topology to cancer stem cells. Cell Cycle. 12:51–66. 2013. View Article : Google Scholar :
29	Lin L, Piao J, Ma Y, Jin T, Quan C, Kong J, Li Y and Lin Z: Mechanisms underlying cancer growth and apoptosis by DEK overexpression in colorectal cancer. PLoS One. 9:e1112602014. View Article : Google Scholar : PubMed/NCBI
30	Datta A, Adelson ME, Mogilevkin Y, Mordechai E, Sidi AA and Trama JP: Oncoprotein DEK as a tissue and urinary biomarker for bladder cancer. BMC Cancer. 11:2342011. View Article : Google Scholar : PubMed/NCBI
31	Wang J, Sun L, Yang M, Luo W, Gao Y, Liu Z, Qiu X and Wang E: DEK depletion negatively regulates Rho/ROCK/MLC pathway in non-small cell lung cancer. J Histochem Cytochem. 61:510–521. 2013. View Article : Google Scholar : PubMed/NCBI
32	Kappes F, Damoc C, Knippers R, Przybylski M, Pinna LA and Gruss C: Phosphorylation by protein kinase CK2 changes the DNA binding properties of the human chromatin protein DEK. Mol Cell Biol. 24:6011–6020. 2004. View Article : Google Scholar : PubMed/NCBI