Annals of Surgical Oncology

, Volume 21, Issue 4, pp 1304–1313 | Cite as

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

  • Wenwei Zhu
  • Lei Guo
  • Bo Zhang
  • Lili Lou
  • Zhenghai Lin
  • Xiaodong Zhu
  • Ning Ren
  • Qiongzhu Dong
  • Qinghai Ye
  • Lunxiu Qin
Hepatobiliary Tumors



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.


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.


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).


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.


Overall Survival Barcelona Clinic Liver Cancer Barcelona Clinic Liver Cancer Staging Barcelona Clinic Liver Cancer Staging System Independent Validation Cohort 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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.

Supplementary material

10434_2013_3445_MOESM1_ESM.docx (243 kb)
Supplementary material 1 (DOCX 243 kb)


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Copyright information

© Society of Surgical Oncology 2013

Authors and Affiliations

  • Wenwei Zhu
    • 1
    • 2
  • Lei Guo
    • 1
    • 2
  • Bo Zhang
    • 1
    • 2
  • Lili Lou
    • 1
  • Zhenghai Lin
    • 1
    • 2
  • Xiaodong Zhu
    • 1
    • 2
  • Ning Ren
    • 1
    • 2
  • Qiongzhu Dong
    • 1
    • 2
  • Qinghai Ye
    • 1
    • 2
  • Lunxiu Qin
    • 1
    • 2
  1. 1.Liver Cancer Institute and Zhongshan HospitalFudan UniversityShanghaiChina
  2. 2.Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of EducationFudan UniversityShanghaiChina

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