PMID- 23874805
OWN - NLM
STAT- MEDLINE
DCOM- 20140213
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 7
DP  - 2013
TI  - Identification of serum monocyte chemoattractant protein-1 and prolactin as 
      potential tumor markers in hepatocellular carcinoma.
PG  - e68904
LID - 10.1371/journal.pone.0068904 [doi]
LID - e68904
AB  - 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(R) 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.
FAU - Wang, Who-Whong
AU  - Wang WW
AD  - Department of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore.
FAU - Ang, Soo Fan
AU  - Ang SF
FAU - Kumar, Rajneesh
AU  - Kumar R
FAU - Heah, Charmain
AU  - Heah C
FAU - Utama, Andi
AU  - Utama A
FAU - Tania, Navessa Padma
AU  - Tania NP
FAU - Li, Huihua
AU  - Li H
FAU - Tan, Sze Huey
AU  - Tan SH
FAU - Poo, Desmond
AU  - Poo D
FAU - Choo, Su Pin
AU  - Choo SP
FAU - Chow, Wan Cheng
AU  - Chow WC
FAU - Tan, Chee Kiat
AU  - Tan CK
FAU - Toh, Han Chong
AU  - Toh HC
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20130718
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Chemokine CCL2)
RN  - 9002-62-4 (Prolactin)
SB  - IM
MH  - Biomarkers, Tumor/*blood
MH  - Carcinoma, Hepatocellular/blood/*diagnosis
MH  - Chemokine CCL2/*blood
MH  - Cohort Studies
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Indonesia
MH  - Liver Neoplasms/blood/*diagnosis
MH  - Prolactin/*blood
MH  - Proteomics
MH  - ROC Curve
MH  - Singapore
PMC - PMC3715515
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/07/23 06:00
MHDA- 2014/02/14 06:00
PMCR- 2013/07/18
CRDT- 2013/07/23 06:00
PHST- 2012/12/17 00:00 [received]
PHST- 2013/05/31 00:00 [accepted]
PHST- 2013/07/23 06:00 [entrez]
PHST- 2013/07/23 06:00 [pubmed]
PHST- 2014/02/14 06:00 [medline]
PHST- 2013/07/18 00:00 [pmc-release]
AID - PONE-D-12-39995 [pii]
AID - 10.1371/journal.pone.0068904 [doi]
PST - epublish
SO  - PLoS One. 2013 Jul 18;8(7):e68904. doi: 10.1371/journal.pone.0068904. Print 2013.