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Melanoma differentiation-associated gene-7/interleukin-24 as a potential prognostic biomarker and second primary malignancy indicator in head and neck squamous cell carcinoma patients

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Tumor Biology

Abstract

The significance of melanoma differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24) expression in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study was designed to investigate and evaluate the clinical significance of MDA-7/IL-24 expression in HNSCC by detecting expression by immunostaining in 131 HNSCC specimens. The function of MDA-7/IL-24 was investigated by real-time polymerase chain reaction (PCR) and Western blot in Ad5.mda-7-infected HNSCC cell lines. Our results showed that MDA-7/IL-24 was mainly expressed in the cytoplasm of HNSCC cells. MDA-7/IL-24 high patients presented with a favorable postoperative prognosis compared with MDA-7/IL-24 low patients, and high expression of MDA-7/IL-24 was significantly correlated with a lower incidence of second primary malignancies (SPMs) in the head and neck regions. In vitro assays showed that high expression of MDA-7/IL-24 could upregulate the expression of the epithelial terminal differentiation markers cytokeratin (KRT) 1, KRT4, KRT13, phosphorylated endoplasmic reticulum stress protein (p)-EIF2a, and the apoptosis-related protein cleaved caspase-3. It also downregulated the epithelial proliferative markers KRT5, KRT14, Integrin β4, and anti-apoptosis protein Bcl-2, which might be partially involved in the underlying mechanisms of Ad.mda-7-mediated HNSCC differentiation and apoptosis. Our results indicate that MDA-7/IL-24 can be a prognostic biomarker and an indicator of second primary malignancies (SPM) in HNSCC.

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Acknowledgments

This study was supported by the 985 special fund for multi-hospitals’ phase III clinical trial in Peking University, the National High Technology Research and Development Program of China (no. 2009AA045201 and no. 2012AA041606), the Special fund for Capital Medical Development (no. 2011-4025-02), and the China Postdoctoral Science Foundation funded project (no. 2013 M530495). The source of replication-deficient adenoviruses used in this study was constructed by the Vector Gene Technology Company Ltd.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian, Beijing, 100081, People’s Republic of China

    Lin Wang, Zhien Feng, Huanhuan Wu, Shuai Zhang, Yinfei Pu, Huan Bian & Chuanbin Guo

  2. Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian, Beijing, 100081, People’s Republic of China

    Yixiang Wang

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  1. Lin Wang
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  2. Zhien Feng
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Correspondence to Yixiang Wang or Chuanbin Guo.

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Wang, L., Feng, Z., Wu, H. et al. Melanoma differentiation-associated gene-7/interleukin-24 as a potential prognostic biomarker and second primary malignancy indicator in head and neck squamous cell carcinoma patients. Tumor Biol. 35, 10977–10985 (2014). https://doi.org/10.1007/s13277-014-2392-0

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  • DOI: https://doi.org/10.1007/s13277-014-2392-0

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