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Preoperative serum retinol-binding protein 4 is associated with the prognosis of patients with hepatocellular carcinoma after curative resection

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Abstract

Purpose

Metabolic syndrome and insulin resistance have been linked to increased risk of occurrence and mortality of hepatocellular carcinoma (HCC). Recently, retinol-binding protein 4 (RBP4) was clarified as a specific serological marker of insulin resistance. The aim of this study was to determine whether serum RBP4 could be used as a potential marker for predicting prognosis in patients with HCC after curative resection.

Methods

Western immunoblotting and Enzyme-linked immunosorbent assay were used to measure the RBP4 expression in cell lines, supernatant, and serum. Serum RBP4 levels were compared with clinicopathological features and outcomes of patients with HCC. Furthermore, we investigated the impact of serum RBP4 level, serum C-peptide level, and HOMA-IR on overall survival (OS) and disease-free survival (DFS) of patients with HCC in the training cohort (156 patients with HCC), and then were validated in the validation cohort (105 patients with HCC).

Results

RBP4 protein overexpressed in HCC cell lines compared with normal liver cell line (P < 0.001) and correlated with metastatic potential. Serum RBP4 levels were associated with OS [hazard ratio (HR) = 2.208, P < 0.001] and DFS (HR = 1.878, P = 0.029) of patients with HCC. By multivariate analysis, the serum RBP4 level was identified as an independent factor for OS (HR = 2.170, P = 0.004) and DFS (HR = 1.769, P = 0.037) of patients with HCC. The prognostic value of serum RBP4 level was confirmed in the validation cohort.

Conclusions

The serum RBP4 level is potential to be a useful prognostic factor for HCC after curative resection.

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Acknowledgments

This study was jointly supported by National Natural Science Funds of China (No. 30973499); National Natural Science Funds of China (No. 30801102); National S&T Major Project (No. 2008ZX10002-026); Dawn Program of Shanghai Education Commission (No. 07SG04).

Conflict of interest statement

None.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Punan Hospital, Shanghai, 200125, China

    Dan-Dan Wang & Ju-** Chen

  2. Department of Gynecology and Obstetrics, Punan Hospital, Shanghai, 200125, China

    Hai-Yan Dai

  3. Department of Radiology, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Guang Ren

  4. Department of Hematology, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China

    Zu-Guang **a

  5. Department of Radiology, Second Affiliated Hospital, Xuzhou Medical College, Xuzhou, 221006, China

    Tao Zhang

  6. Department of Radiology, Tenth People’s Hospital, Tongji University, Shanghai, 200072, China

    Fei Wang & Guang-Yu Tang

  7. Gynecology and Obstetrics Institute, Gynecology and Obstetrics Hospital, Fudan University, Shanghai, 200011, China

    Wei Zhang

  8. Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, China

    Yi-Ming Zhao, Lu Wang, **-Long Wang, Qi Pan, Zhi Dai, Hong-Wei He, Jia-Min Zhou, Jian Zhou, Jia Fan & Zhao-You Tang

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  1. Dan-Dan Wang
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Corresponding authors

Correspondence to Lu Wang or Guang-Yu Tang.

Additional information

D.-D. Wang, Y.-M. Zhao, G. Ren, F. Wang, and Z.-G. **a contributed equally to this work.

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Supplementary material 1 (DOCX 15 kb)

432_2010_927_MOESM2_ESM.tif

Supplemental Fig. S1 In training cohort, Stratified survival curve were drawn according to absence or presence of liver cirrhosis (A-D) and TNM stage (E-H) to further investigate the prognostic value of serum RBP4 in HCC patients (TIFF 1048 kb)

432_2010_927_MOESM3_ESM.tif

Supplemental Fig. S2 With the cutoff used in training cohort, prognostic significance of serum RBP4 level for OS (A) and DFS (B) were confirmed in the validation cohort (TIFF 262 kb)

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Wang, DD., Zhao, YM., Wang, L. et al. Preoperative serum retinol-binding protein 4 is associated with the prognosis of patients with hepatocellular carcinoma after curative resection. J Cancer Res Clin Oncol 137, 651–658 (2011). https://doi.org/10.1007/s00432-010-0927-3

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  • DOI: https://doi.org/10.1007/s00432-010-0927-3

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