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Overexpression of S100A4 Predicts Migration, Invasion, and Poor Prognosis of Hypopharyngeal Squamous Cell Carcinoma

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Abstract

Introduction

Hypopharyngeal squamous cell carcinoma (HSCC) is among the most lethal tumors encountered in the head and neck and frequently involves regional metastasis. However, the mechanism underlying the aggressiveness of HSCC remains elusive. S100A4 is a well-established metastasis-promoting regulator in a variety of malignancies, but its role in HSCC has not yet been identified.

Objectives

Our objectives were to explore the expression levels of S100A4 in HSCC tumors and its association with clinicopathological parameters and the clinical prognosis of HSCC and to confirm its role in the metastatic process of the HSCC FaDu cell line in vitro.

Methods

We assessed the expression levels of S100A4 with immunohistochemistry (IHC) in HSCC tumors (n = 71) and adjacent normal tissues (n = 44). In vitro experiments were performed to explore the impact of S100A4 knockdown on biological phenotypes of human HSCC FaDu cell line, including migration, invasion, proliferation, apoptosis, and cell cycle.

Results

The expression of S100A4 was elevated in HSCC tumors compared with adjacent normal tissues and positively correlated with cervical lymph node metastasis in this HSCC patient cohort. In vitro experiments showed that S100A4 knockdown significantly impaired migration and invasion and increased the proportion of cells in G0/G1 phase with no change in proliferation or apoptosis in FaDu cells. Additionally, nuclear S100A4 expression proved to be an independent prognostic indicator in patients with HSCC.

Conclusion

This study demonstrated for the first time that S100A4 expression is upregulated in HSCC tumors and that this upregulation is positively correlated with cervical lymph node metastasis of this malignancy. The metastasis-promoting role of S100A4 was further validated in the HSCC FaDu cell line, indicating that S100A4 is a potential therapeutic target for HSCC. Furthermore, this study suggests that nuclear S100A4 expression could be considered a prognostic biomarker for HSCC.

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Authors and Affiliations

  1. NHC Key Laboratory of Otorhinolaryngology, Department of Otorhinolaryngology, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, China

    Jianing Xu, Shengda Cao, Dapeng Lei & Xinliang Pan

  2. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Neil Gross

  3. Department of Urology,Qilu Hospital, Shandong University, Jinan, Shandong, 250012, China

    Yuanwei Zang & Feilong Yang

  4. Key Laboratory of Otolaryngology Head and Neck Surgery, Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Beijing Institute of Otolaryngology, Ministry of Education, Capital Medical University, Beijing, 100730, China

    Zheng Yang

  5. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Head and Neck Surgery, Peking University Cancer Hospital and Institute, Beijing, China

    Wenbin Yu

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  1. Jianing Xu
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  2. Neil Gross
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  3. Yuanwei Zang
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  9. Xinliang Pan
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Corresponding authors

Correspondence to Wenbin Yu or Xinliang Pan.

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Conflicts of interest

J Xu, N. Gross, Y. Zang, S. Cao, F. Yang, Z. Yang, W. Yu, D. Lei, X. Pan have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

This study protocol was approved by the Ethics Committee of Qilu Hospital of Shandong University.

Informed consent

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

Funding

This work was supported by the Taishan Scholars Program (No. tshw20130950), Shandong Province, and the Department of Science & Technology of Shandong Province (Nos. ZR2013HM107, ZR2014HM005, 2015GSF118014, 2015GSF118030 and 2018GSF18166), and Science Foundation of Qilu Hospital of Shandong University; and the Fundamental Research Funds of Shandong University (No. 2014QLKY05).

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Xu, J., Gross, N., Zang, Y. et al. Overexpression of S100A4 Predicts Migration, Invasion, and Poor Prognosis of Hypopharyngeal Squamous Cell Carcinoma. Mol Diagn Ther 23, 407–417 (2019). https://doi.org/10.1007/s40291-019-00393-2

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  • DOI: https://doi.org/10.1007/s40291-019-00393-2

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