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Stromal expression of JNK1 and VDR is associated with the prognosis of esophageal squamous cell carcinoma

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Abstract

Purpose

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide, and its outcome is poor. The purpose of this study was to determine the association between JNK1 and vitamin D receptor (VDR) expression and the prognosis of ESCC.

Methods

Immunohistochemical staining was conducted on ESCC tissue microarrays (362 pairs of ESCC and normal esophagus tissues). The epithelial and stromal expression levels of c-jun NH2-terminal kinase 1 (JNK1) and VDR were scored and correlated with the ESCC characteristics. Laser-capture-based quantitative RT-PCR was performed on ESCC tissues. The effects of JNK1 and VDR on ESCC cell proliferation and migration were analyzed in vitro by transient transfection, and protein changes were evaluated by immunoblotting.

Results

Both JNK1 and VDR were reduced in ESCC epithelial cells in comparison with the normal esophagus, but the expression of JNK1 and VDR in ESCC stromal tissues, not epithelial cells, was strongly associated with the survival time of ESCC patients. Functional studies showed that increased JNK1 suppressed cancer cell proliferation, mobility, and migration, which were linked to the alterations of VDR and metastasis-associated proteins.

Conclusion

JNK1 and VDR act as tumor suppressors, and their stromal expression levels are associated with prognosis in esophageal squamous cell carcinoma.

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Abbreviations

JNK1:

c-jun NH2-terminal kinase 1

VDR:

Vitamin D receptor

ESCC:

Esophageal squamous cell carcinoma

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Acknowledgements

This work was supported, in part, by a grant from the US Chinese Anti-cancer Association (USCACA-TIGM-001 to Yang W) and a Startup fund from Jining Medical University (to Bao Y and Guo Y). We would like to thank Dr. Virgilia Macias and Mr. Ryan Deaton from Research Histology and Tissue Imaging Core (RHTIC) of the Research Resources Center of University of Illinois at Chicago for technical assistance.

Author information

Authors and Affiliations

  1. Department of Pathology and Institute of Precision Medicine, Jining Medical University, 16 Hehua Road, Jining, 272067, China

    Y. Bao, Y. Guo, X. Wei, Y. Yang & W. Yang

  2. Department of Pathology, Xinxiang Medical University, Xinxiang, China

    S. Zhang, Y. Zhang & H. Zhang

  3. Department of Surgery, Affiliated Hospital, Jining Medical University, Jining, China

    M. Ma

  4. Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA

    W. Yang

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  1. Y. Bao
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  4. X. Wei
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  5. Y. Zhang
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Correspondence to W. Yang.

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The authors declare no conflict of interest.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee as well as with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Not applicable to this study.

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Bao, Y., Zhang, S., Guo, Y. et al. Stromal expression of JNK1 and VDR is associated with the prognosis of esophageal squamous cell carcinoma. Clin Transl Oncol 20, 1185–1195 (2018). https://doi.org/10.1007/s12094-018-1843-2

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  • DOI: https://doi.org/10.1007/s12094-018-1843-2

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