Identification of serum monocyte chemoattractant protein-1 and prolactin as potential tumor markers in hepatocellular carcinoma

PLoS One. 2013 Jul 18;8(7):e68904. doi: 10.1371/journal.pone.0068904. Print 2013.

Abstract

Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)), confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC) indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001). In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients' sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as potential biomarker on a larger scale in patients at-risk of HCC.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / diagnosis*
  • Chemokine CCL2 / blood*
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Indonesia
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis*
  • Prolactin / blood*
  • Proteomics
  • ROC Curve
  • Singapore

Substances

  • Biomarkers, Tumor
  • Chemokine CCL2
  • Prolactin

Grant support

Study of the SGH cohort in this research was supported by grants awarded by the National Medical Research Council (NMRC), Ministry of Health, Republic of Singapore (NMRC/1191/2008 and NMRC/IBG/NCC/2009; http://www.nmrc.gov.sg/content/nmrc_internet/home.html). Study of the MRIN cohort was supported by the institutional funding of MRIN (http://www.mrinstitute.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.