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B7-H3 is expressed in human hepatocellular carcinoma and is associated with tumor aggressiveness and postoperative recurrence

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Abstract

B7-H3, a novel B7 family member, positively or negatively regulates T-cell responses. We investigated the clinical relevance and prognostic significance of B7-H3 in hepatocellular carcinoma (HCC). Western blotting showed B7-H3 upregulation in 17 of 24 (70.8 %) HCC tissues compared with nontumor liver tissues (p = 0.028). B7-H3 immunostaining on tissue microarrays containing 240 HCC patient samples indicated that 225 (93.8 %) tumors had aberrant B7-H3 expression, with strong intensity in 79 (32.9 %) cases, whereas B7-H3 expression in peritumor liver cells was weak in most cases (226; 94.2 %). Notably, patients with high/moderate tumor cell B7-H3 expression showed significantly poorer survival (p = 0.009) and increased recurrence (p = 0.002). After multivariable adjustment, high/moderate B7-H3 expression remained significant for an increased risk of recurrence (hazard ratio = 1.79; 95 % confidence interval = 1.19–2.70; p = 0.005). B7-H3 expression correlated with invasive phenotypes like vascular invasion and advanced tumor stage, and the metastatic potential of HCC cell lines. Flow cytometry showed that B7-H3 expression is inversely correlated with proliferation and interferon-γ production by infiltrating T cells. Interferon-γ stimulation significantly upregulated B7-H3 expression in HCC cells in vitro, implicating B7-H3 expression as a feedback mechanism to evade anti-tumor immunity. Importantly, the prognostic value of B7-H3 expression was validated in an independent cohort of 206 HCC patients. Collectively, our data suggest that B7-H3 was abundantly expressed in HCC and was associated with adverse clinicopathologic features and poor outcome. Thus, B7-H3 represents an attractive target for diagnostic and therapeutic manipulation in human HCC.

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Abbreviations

HCC:

Hepatocellular carcinoma

TNM:

Tumor-node-metastasis

SD:

Standard deviation

OS:

Overall survival

TIL:

Tumor-infiltrating lymphocytes

HR:

Hazard ratio

CI:

Confidence interval

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Acknowledgments

This study was supported by the Major Program of NSFC (No.81030038), National Key Sci-Tech Project (2008ZX10002-019), Shanghai Rising-Star Program (No. 10QA1401300), National Natural Science Foundation of China (No. 30872379 & No. 30901432), and “Chen Guang” project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (No. 11CG02).

Conflict of interest

The authors declare no competing interests to this paper.

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Authors and Affiliations

  1. Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, 180 Feng Lin Road, Shanghai, 200032, People’s Republic of China

    Tai-Wei Sun, Qiang Gao, Shuang-Jian Qiu, Jian Zhou, Xiao-Ying Wang, Yong Yi, Jie-Yi Shi, Ying-Hong Shi, Kang Song, Yong-Sheng Xiao & Jia Fan

  2. Institute of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China

    Jian Zhou & Jia Fan

  3. Department of Pancreas and Hepatobiliary Surgery, Cancer Hospital and Shanghai Medical School, Fudan University, Shanghai, People’s Republic of China

    Yong-Feng Xu

  4. Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People’s Republic of China

    Tai-Wei Sun, Qiang Gao, Shuang-Jian Qiu, Jian Zhou, Xiao-Ying Wang, Yong Yi, Jie-Yi Shi, Ying-Hong Shi, Kang Song, Yong-Sheng Xiao & Jia Fan

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  1. Tai-Wei Sun
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Correspondence to Jia Fan.

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Tai-Wei Sun, Qiang Gao, and Shuang-Jian Qiu contributed equally to this work.

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Sun, TW., Gao, Q., Qiu, SJ. et al. B7-H3 is expressed in human hepatocellular carcinoma and is associated with tumor aggressiveness and postoperative recurrence. Cancer Immunol Immunother 61, 2171–2182 (2012). https://doi.org/10.1007/s00262-012-1278-5

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