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Elevated serum soluble CD14 levels in chronic HBV infection are significantly associated with HBV-related hepatocellular carcinoma

  • Original Article
  • Published:
Tumor Biology

Abstract

Hepatitis B virus (HBV) infection is a major cause of chronic liver diseases including hepatocellular carcinoma (HCC). CD14 and its soluble form sCD14 play important roles in immunity and are involved in the translocation of bacteria and their products which is related to the pathogenesis in chronic HBV infection. This study investigated serum sCD14 levels in HBV chronically infected patients with various clinical diseases. Serum sCD14 levels in HBV patients were significantly elevated compared with those of healthy controls. HCC patients had significantly highest levels of serum sCD14 across all the HBV-related diseases. Serum sCD14 levels significantly discriminated HCC from other HBV-related non-HCC diseases. The area under the receiver operating characteristic curve (AUC) of sCD14 levels for HCC was significantly higher in comparison with other HBV-related non-HCC diseases. The AUC of sCD14 for HCC (0.868, 95 % CI 0.791–0.946, P < 0.001) was higher than that of alpha-fetoprotein (0.660, 95 % CI 0.508–0.811, P = 0.039). Serum level of sCD14 was associated with the overall survival (OS) of HCC patients, with sCD14 levels >20 ng/mL being significantly related to poorer OS (P = 0.017). Multivariate regression showed that serum sCD14 level was an independent factor associated with the OS rates of HBV-related HCC patients (HR 2.544, 95 % CI 1.169–5.538, P = 0.019). HCC resection resulted in a significant decrease of sCD14 levels (P < 0.001). These findings suggest the potential role of sCD14 in the pathogenesis of chronic HBV infection, especially the development of HCC, and the potential usefulness of sCD14 as a biomarker for discriminating clinical diseases and predicting survival of HCC patients in chronic HBV infection.

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Abbreviations

AFP:

Alpha-fetoprotein

ALT:

Alanine aminotransferase

ASC:

Asymptomatic HBV carrier status

AST:

Aspartate aminotransferase

AUC:

Area under the ROC curve

CH:

Chronic hepatitis

CT:

Computerized tomography

CI:

Confidence interval

CV:

Coefficient of variation

ELISA:

Enzyme-linked immunosorbent assay

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HIV:

Human immunodeficiency virus

HR:

Hazard ratio

IL:

Interleukin

LC:

Liver cirrhosis

LPS:

Lipopolysaccharide

MDD:

Minimum detectable dose

MRI:

Magnetic resonance imaging

mCD14:

Membrane CD14

OS:

Overall survival

ROC curve:

Receiver operating characteristic curve

sCD14:

Soluble CD14

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-α

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Acknowledgments

This work was supported in part by funding from the National Natural Science Foundation of China (grant no. 81371798). The authors are indebted to Dr. Guoyu Zhang and Dr. Zhu Li for their help in this study.

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Authors and Affiliations

  1. Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, 710061, Shaanxi, China

    Na Li, Qianqian Zhu, Cuiling Yang, Fang Li, Zhihua Zhou, Jiao Sang, Qunying Han & Zhengwen Liu

  2. Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    Yi Lv

  3. Institute of Advanced Surgical Technology and Engineering, Xi’an Jiaotong University, Xi’ an, 710061, Shaanxi, China

    Yi Lv & Zhengwen Liu

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  1. Na Li
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  4. Fang Li
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Li, N., Zhu, Q., Yang, C. et al. Elevated serum soluble CD14 levels in chronic HBV infection are significantly associated with HBV-related hepatocellular carcinoma. Tumor Biol. 37, 6607–6617 (2016). https://doi.org/10.1007/s13277-015-4423-x

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  • DOI: https://doi.org/10.1007/s13277-015-4423-x

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