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Combination of Osteopontin with Peritumoral Infiltrating Macrophages is Associated with Poor Prognosis of Early-Stage Hepatocellular Carcinoma after Curative Resection

  • Hepatobiliary Tumors
  • Published:
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Abstract

Background

Crosstalk between a tumor and the microenvironment plays a key role in tumor progression and metastasis. This study was performed to elucidate the prognostic significance of combining tumor-secreted osteopontin (OPN) with microenvironment-associated peritumoral macrophages (PTMs) in hepatocellular carcinoma (HCC), especially for those with early-stage disease.

Methods

Tissue microarray-based immunohistochemistry was used to investigate OPN and PTMs expression in two independent cohorts consisting of 374 patients with HCC who underwent radical resection. The prognostic value for the two factors alone or in combination was investigated in these patients.

Results

OPN combined with PTMs was an independent prognostic factor for both overall survival (OS; p < 0.0001) and time to recurrence (TTR; p = 0.003) from the learning cohort (n = 96). Their combined value for prognosis was validated in early-stage HCCs using another independent cohort (n = 278; OS, p < 0.001; TTR, p = 0.001). This combination remained significant in HCCs with low α-fetoprotein levels in both cohorts, and was predictive for early recurrence/death risk (<2 years) compared with a single marker. Only OPN+HCCs had a significant correlation of PTMs levels with OS (p = 0.01) or TTR (p = 0.011).

Conclusions

Tumor OPN combined with PTMs is a promising predictor of tumor recurrence and survival in patients with HCC, especially for those with early-stage disease. The interplay of OPN and PTMs represents a new insight into tumor progression and therapeutic targets for HCC.

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Acknowlegdment

This work was supported in part by grants from the National Key Project for Infectious Disease of China (2012ZX10002012-003), the State Key Basic Research Program of China (2009CB521701), the “973” State Key Basic Research Program of China (2014CB542101) and the National Natural Science Foundation of China (81071993, 30672037, 30300400, and 30700991).

Conflict of interest

The authors made no disclosures.

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Authors and Affiliations

  1. Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China

    Wenwei Zhu MD, Lei Guo MD, Bo Zhang MD, Lili Lou MD, Zhenghai Lin MD, PhD, Xiaodong Zhu MD, PhD, Ning Ren MD, PhD, Qiongzhu Dong PhD, Qinghai Ye MD, PhD & Lunxiu Qin MD, PhD

  2. Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China

    Wenwei Zhu MD, Lei Guo MD, Bo Zhang MD, Zhenghai Lin MD, PhD, Xiaodong Zhu MD, PhD, Ning Ren MD, PhD, Qiongzhu Dong PhD, Qinghai Ye MD, PhD & Lunxiu Qin MD, PhD

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  1. Wenwei Zhu MD
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  2. Lei Guo MD
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  3. Bo Zhang MD
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  4. Lili Lou MD
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  5. Zhenghai Lin MD, PhD
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  8. Qiongzhu Dong PhD
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Corresponding author

Correspondence to Qinghai Ye MD, PhD.

Additional information

Wenwei Zhu, Lei Guo, and Bo Zhang contributed equally to this work.

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Zhu, W., Guo, L., Zhang, B. et al. Combination of Osteopontin with Peritumoral Infiltrating Macrophages is Associated with Poor Prognosis of Early-Stage Hepatocellular Carcinoma after Curative Resection. Ann Surg Oncol 21, 1304–1313 (2014). https://doi.org/10.1245/s10434-013-3445-0

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  • DOI: https://doi.org/10.1245/s10434-013-3445-0

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