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B7-H4 expression associates with cancer progression and predicts patient’s survival in human esophageal squamous cell carcinoma

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Abstract

A retrospective cohort study including 112 patients suffering from esophageal squamous cell carcinoma (ESCC) was performed to investigate the expression of B7-H4 in ESCC and determine its association with patient’s clinicopathological parameters and survival. Expression levels of B7-H4 on tumor cells and densities of tumor infiltrating lymphocytes (TILs) in the surgical specimens of ESCC tissues were characterized using immunohistochemical assays. Uni- and multivariate analyses were performed to evaluate the prognostic value of B7-H4 expression levels and densities of TILs in tumor sections. Positive B7-H4 immunostaining was observed in 107 of 112 (95.5%) of ESCC tissue sections. We further divided all patients into two major subgroups, a lower B7-H4 expression group with 46 patients and a higher B7-H4 expression group with 66 patients. We found that expression levels of B7-H4 on tumor cells were significantly correlated with patient’s gender (P = 0.0288), distant metastasis (P = 0.0500), and TNM stage (P = 0.0258). Moreover, tumor cell B7-H4 expression was inversely correlated with densities of CD3+ T cells in tumor nest (P = 0.0424) and CD8+ T cells in tumor stroma (P = 0.0229). The overall survival rate of the patients with higher B7-H4 expression was significantly worse than that of the patients with lower B7-H4 expression (P = 0.0105, Hazard Ratio: 1.854, 95%CI:1.152–2.902). Markers of cell-mediated immune responses such as CD3, CD8, and T-bet were associated with better patient survival. The present study demonstrated that B7-H4 expression in human ESCC is associated with cancer progression, reduced tumor immunosurveillance and worse patient outcomes. B7-H4 can serve as a novel prognostic predictor for human ESCC and a potential target for the immune therapy against this malignancy.

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Acknowledgments

We thank senior pathologists Chang-qing Lu, Qing Li, Bo Tian, Jun Xie, Cao Wu, Yuan-dong Chen and Prof. Tong-yu Chen (Department of Pathology, the Third Affiliated Hospital of Suzhou University, Jiangsu Changzhou, China) for their expert suggestions and technical assistances. This work was supported by grants from the Major State Basic Research Development Program of China (973 Program: CB51003), the National Natural Science Foundation of China (No. 30930085), and the advanced program of Commission of Technology and Industry for National Defense (A3820060130).

Conflict of interest

The authors declare that they have no competing interests to this paper.

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Authors and Affiliations

  1. Institute of Medical Biotechnology, Medical College of Suzhou University, 708 Renmin Road, 215007, Suzhou, Jiangsu, China

    Lu-jun Chen, Jing Sun & Xue-guang Zhang

  2. Clinical Immunology Laboratory, The First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu, China

    Hong-ya Wu

  3. Department of Tumor Biological Treatment, Yixing Tumor Hospital, Wuxi, Jiangsu, China

    Shu-ming Zhou & Ming Tan

  4. Department of Pathology, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China

    Yan Tan

  5. Tumor Research Institute, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

    Bao-en Shan

  6. Department of Immunology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    Bin-feng Lu

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  1. Lu-jun Chen
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  2. Jing Sun
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Correspondence to Bin-feng Lu or Xue-guang Zhang.

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L. Chen and J. Sun contributed equally to this work.

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Chen, Lj., Sun, J., Wu, Hy. et al. B7-H4 expression associates with cancer progression and predicts patient’s survival in human esophageal squamous cell carcinoma. Cancer Immunol Immunother 60, 1047–1055 (2011). https://doi.org/10.1007/s00262-011-1017-3

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  • DOI: https://doi.org/10.1007/s00262-011-1017-3

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