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Clinicopathological significance of orphan nuclear receptor Nurr1 expression in gastric cancer

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Abstract

Background

Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related deaths worldwide. Gastric cancer is characterized by high levels of invasion and metastasis. Increasing attention is being focused on discovering molecular markers for the diagnosis of gastric cancer and for predicting its prognosis. The objective of the present study was to evaluate Nurr1 expression in gastric cancer and to assess its correlation with clinicopathological parameters and prognosis in gastric cancer patients.

Methods

Tissue samples were obtained from 120 gastric cancer patients. We investigated Nurr1 expression in human normal and gastric cancer tissues using real-time reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. We determined the association between Nurr1 and recurrence, prognosis and patient clinicopathological parameters. Univariate and multivariate survival analyses with a Cox’s proportional hazards regression model were used to identify independent factors related to recurrence and prognosis.

Results

The immunohistochemical, qRT-PCR and western blot analyses revealed that Nurr1 expression was increased in gastric cancer tissues compared with normal gastric tissue (P < 0.05). Nurr1 expression was significantly correlated with the tumor size, depth of tumor invasion, lymph node metastasis, recurrence, and distant metastasis of gastric cancer (P < 0.05). Moreover, Nurr1-high patients also exhibited poorer overall survival (OS) and disease-free survival compared with Nurr1-low patients (P < 0.01). The univariate and multivariate survival analyses suggested that Nurr1 expression (P = 0.011), histology (P = 0.018), depth of tumor invasion (P = 0.037), and presence of lymph node metastasis (P = 0.031) were independent prognostic factors for recurrence. In addition, Nurr1 expression (P = 0.007), depth of tumor invasion (P = 0.014), lymph node metastasis (P = 0.044), distant metastasis (P = 0.023), and recurrence (P = 0.011) were independent prognostic factors of OS in gastric cancer patients.

Conclusions

The Nurr1 protein may be useful as a marker of recurrence, metastasis, and poor prognosis following curative resection in patients with gastric cancer.

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References

  1. Bertuccio P, Chatenoud L, Levi F, Praud D, Ferlay J, Negri E, et al. Recent patterns in gastric cancer: a global overview. Int J Cancer. 2009;125(3):666–73.

    Article  CAS  PubMed  Google Scholar 

  2. Bosetti C, Bertuccio P, Malvezzi M, Levi F, Chatenoud L, Negri E, et al. Cancer mortality in Europe, 2005–2009, and an overview of trends since 1980. Ann Oncol. 2013;24(10):2657–71.

    Article  CAS  PubMed  Google Scholar 

  3. Ferro A, Peleteiro B, Malvezzi M, Bosetti C, Bertuccio P, Levi F, et al. Worldwide trends in gastric cancer mortality (1980–2011), with predictions to 2015, and incidence by subtype. Eur J Cancer. 2014;50(7):1330–44.

    Article  PubMed  Google Scholar 

  4. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008 v2.0, Cancer incidence and mortality worldwide: IARC Cancer Base No. 10. http://globocan.iarc.fr, 2010. Accessed 15 June 2013.

  5. Shen L, Shan YS, Hu HM, Price TJ, Sirohi B, Yeh KH, et al. Management of gastric cancer in Asia: resource-stratified guidelines. Lancet Oncol. 2013;14(12):e535–47.

    Article  PubMed  Google Scholar 

  6. Sekiguchi M, Suzuki H, Oda I, Abe S, Nonaka S, Yoshinaga S, et al. Risk of recurrent gastric cancer after endoscopic resection with a positive lateral margin. Endoscopy. 2014;46(4):273–8.

    Article  PubMed  Google Scholar 

  7. Wallén A, Zetterström RH, Solomin L, Arvidsson M, Olson L, Perlmann T. Fate of mesencephalic AHD2-expressing dopamine progenitor cells in NURR1 mutant mice. Exp Cell Res. 1999;253(2):737–46.

    Article  PubMed  Google Scholar 

  8. Llopis S, Singleton B, Duplessis T, Carrier L, Rowan B, Williams C. Dichotomous roles for the orphan nuclear receptor NURR1 in breast cancer. BMC Cancer. 2013;13:139.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Inamoto T, Czerniak BA, Dinney CP, Kamat AM. Cytoplasmic mislocalization of the orphan nuclear receptor Nurr1 is a prognostic factor in bladder cancer. Cancer. 2010;116(2):340–6.

    Article  PubMed  Google Scholar 

  10. Wang J, Yang J, Zou Y, Huang GL, He ZW. Orphan nuclear receptor nurr1 as a potential novel marker for progression in human prostate cancer. Asian Pac J Cancer Prev. 2013;14(3):2023–8.

    Article  PubMed  Google Scholar 

  11. Holla Vijaykumar R, Mann Jason R. Qiong. Prostaglandin E2 regulates the nuclear receptor NR4A2 in colorectal cancer. J Biol Chem. 2006;281(5):2676–82.

    Article  CAS  PubMed  Google Scholar 

  12. Nomura E, Lee SW, Bouras G, Tokuhara T, Hayashi M, Hiramatsu M, et al. Functional outcomes according to the size of the gastric remnant and type of reconstruction following laparoscopic distal gastrectomy for gastric cancer. Gastric Cancer. 2011;14(3):279–84.

    Article  PubMed  Google Scholar 

  13. Deutsch AJ, Angerer H, Fuchs TE, Neumeister P. The nuclear orphan receptors NR4A as therapeutic target in cancer therapy. Anticancer Agents Med Chem. 2012;12(9):1001–14.

    Article  CAS  PubMed  Google Scholar 

  14. Wang J, Yang J, Li BB, He ZW. High cytoplasmic expression of the orphan nuclear receptor NR4A2 predicts poor survival in nasopharyngeal carcinoma. Asian Pac J Cancer Prev. 2013;14(5):2805–9.

    Article  PubMed  Google Scholar 

  15. Inamoto T, Czerniak BA, Dinney CP, Kamat AM. Cytoplasmic mislocalization of the orphan nuclear receptor Nurr1 is a prognostic factor in bladder cancer. Cancer. 2010;116(2):340–6.

    Article  PubMed  Google Scholar 

  16. Boakye CH, Doddapaneni R, Shah PP, Patel AR, Godugu C, Safe S, et al. Chemoprevention of skin cancer with 1,1-Bis (3′-indolyl)-1-(aromatic) methane analog through induction of the orphan nuclear receptor, NR4A2 (Nurr1). PLoS ONE. 2013;8(8):e69519.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Zhang T, Wang P, Ren H, Fan J, Wang G. NGFI-B nuclear orphan receptor Nurr1 interacts with p53 and suppresses its transcriptional activity. Mol Cancer Res. 2009;7(8):1408–15.

    Article  CAS  PubMed  Google Scholar 

  18. Imam SZ, Jankovic J, Ali SF, Skinner JT, Xie W, Conneely OM, et al. Nitric oxide mediates increased susceptibility to dopaminergic damage in Nurr1 heterozygous mice. FASEB J. 2005;19(11):1441–50.

    Article  CAS  PubMed  Google Scholar 

  19. Zhao D, Desai S, Zeng H. VEGF stimulates PKD-mediated CREB-dependent orphan nuclear receptor Nurr1 expression: role in VEGF-induced angiogenesis. Int J Cancer. 2011;128(11):2602–12.

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest

There are no conflict of interests to disclose.

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Authors and Affiliations

  1. Department of Surgical Operation, Dalian Medical University, Dalian, 116044, People’s Republic of China

    J. Guo

  2. Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116027, People’s Republic of China

    G. Zu

  3. Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China

    T. Zhou

  4. Department of General Surgery, The Maternity and Child Care Institute of Dalian Xigang District, Dalian, 116021, People’s Republic of China

    J. Xing

  5. Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China

    Z. Wang

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  1. J. Guo
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  2. G. Zu
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  3. T. Zhou
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  4. J. Xing
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  5. Z. Wang
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Corresponding author

Correspondence to Z. Wang.

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G. Zu is co-first author.

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Guo, J., Zu, G., Zhou, T. et al. Clinicopathological significance of orphan nuclear receptor Nurr1 expression in gastric cancer. Clin Transl Oncol 17, 788–794 (2015). https://doi.org/10.1007/s12094-015-1305-z

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  • DOI: https://doi.org/10.1007/s12094-015-1305-z

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