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Tumor Biology

, Volume 37, Issue 5, pp 6607–6617 | Cite as

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

  • Na Li
  • Qianqian Zhu
  • Cuiling Yang
  • Fang Li
  • Zhihua Zhou
  • Yi Lv
  • Jiao Sang
  • Qunying Han
  • Zhengwen Liu
Original Article

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.

Keywords

Hepatitis B virus infection Soluble CD14 Hepatocellular carcinoma Diagnosis Prognosis 

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

Notes

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.

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

13277_2015_4423_MOESM1_ESM.doc (34 kb)
Table S1 (DOC 34 kb)
13277_2015_4423_MOESM2_ESM.doc (32 kb)
Table S2 (DOC 31 kb)
13277_2015_4423_MOESM3_ESM.doc (88 kb)
Fig. S1 (DOC 87 kb)
13277_2015_4423_MOESM4_ESM.doc (114 kb)
Fig. S2 (DOC 114 kb)
13277_2015_4423_MOESM5_ESM.doc (100 kb)
Fig. S3 (DOC 100 kb)
13277_2015_4423_MOESM6_ESM.doc (66 kb)
Fig. S4 (DOC 65 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Na Li
    • 1
  • Qianqian Zhu
    • 1
  • Cuiling Yang
    • 1
  • Fang Li
    • 1
  • Zhihua Zhou
    • 1
  • Yi Lv
    • 2
    • 3
  • Jiao Sang
    • 1
  • Qunying Han
    • 1
  • Zhengwen Liu
    • 1
    • 3
  1. 1.Department of Infectious DiseasesFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  2. 2.Department of Hepatobiliary SurgeryFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  3. 3.Institute of Advanced Surgical Technology and EngineeringXi’an Jiaotong UniversityXi’ anChina

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