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The opposite prognostic significance of nuclear and cytoplasmic p21 expression in resectable gastric cancer patients

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Abstract

Background

Protein p21Cip1/Waf1 is a cyclin-dependent kinase inhibitor, which plays important roles in cell cycle arrest, senescence, and apoptosis. Interestingly, the nuclear and cytoplasmic p21 executes various functions in the cell. In this study, we investigated the prognostic impact of subcellular p21 expression in gastric cancer (GC).

Methods

Expressions of subcellular p21 was assessed by immunohistochemistry using a tissue microarray in a training cohort and it went into a second testing cohort and finally to a validating cohort. Prognostic and predictive role of subcellular p21 expression status was evaluated. We also studied the roles of subcellular p21 in GC cell migration and invasion.

Results

Nuclear and cytoplasmic p21 protein levels were significantly reduced and increased in GC lesions compared with adjacent non-cancerous tissues, respectively. Low nuclear p21 or high cytoplasmic p21 expression significantly correlated with shorter overall survival (OS), as well as with clinicopathologic characteristics in patients. Multivariate regression analysis showed that low nuclear and high cytoplasmic p21 expression, separately and together, were independent negative markers of OS. Finally, we found that nuclear p21 inhibits but cytoplasmic p21 promotes cell migration and invasion abilities.

Conclusions

These findings suggest that nuclear and cytoplasmic p21 protein expression in tumor are novel candidate prognostic markers in resectable human gastric carcinoma, and they exert distinct roles in cell migration and invasion.

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Acknowledgments

This project is supported by the National Natural Science Foundation of China (#81370078, #81001231, #81161120537, and #30930080), the Natural Science Foundation of Jiangsu Province (#BK2012840), the Postdoctoral Science Foundation of China (#20100481165), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, People’s Republic of China

    Yefei Huang, Yansu Chen, Yulin Huang, Jianbing Zhang, Aiping Li, Shouyu Wang & Jianwei Zhou

  2. Department of Oncology, Yixing People’s Hospital, 75 Zhenguan Road, Yixing, 214200, Jiangsu, People’s Republic of China

    Weimin Wang, Yongfei Tan & Yan Zhou

  3. Department of Pathology, Nantong Cancer Hospital, Nantong, 226361, People’s Republic of China

    Jianbing Zhang, Song He & Fulin Qiang

  4. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491, Trondheim, Norway

    Oluf Dimitri Røe

  5. Cancer Clinic, Levanger Hospital, Nord-Trøndelag Health Trust, 7600, Levanger, Norway

    Oluf Dimitri Røe

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  1. Yefei Huang
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  2. Weimin Wang
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  3. Yansu Chen
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  4. Yulin Huang
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  8. Fulin Qiang
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  9. Aiping Li
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  10. Oluf Dimitri Røe
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  11. Shouyu Wang
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  12. Yan Zhou
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  13. Jianwei Zhou
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Corresponding authors

Correspondence to Shouyu Wang or Yan Zhou.

Additional information

Y. Huang, W. Wang and Y. Chen contributed equally to this work.

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Huang, Y., Wang, W., Chen, Y. et al. The opposite prognostic significance of nuclear and cytoplasmic p21 expression in resectable gastric cancer patients. J Gastroenterol 49, 1441–1452 (2014). https://doi.org/10.1007/s00535-013-0900-4

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  • DOI: https://doi.org/10.1007/s00535-013-0900-4

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