title: Identification of serum monocyte chemoattractant protein-1 and prolactin as potential tumor markers in hepatocellular carcinoma.
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.
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
authors.forename: Who-Whong
authors.initials: WW
authors.lastname: Wang
authors.forename: Soo Fan
authors.initials: SF
authors.lastname: Ang
authors.forename: Rajneesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Charmain
authors.initials: C
authors.lastname: Heah
authors.forename: Andi
authors.initials: A
authors.lastname: Utama
authors.forename: Navessa Padma
authors.initials: NP
authors.lastname: Tania
authors.forename: Huihua
authors.initials: H
authors.lastname: Li
authors.forename: Sze Huey
authors.initials: SH
authors.lastname: Tan
authors.forename: Desmond
authors.initials: D
authors.lastname: Poo
authors.forename: Su Pin
authors.initials: SP
authors.lastname: Choo
authors.forename: Wan Cheng
authors.initials: WC
authors.lastname: Chow
authors.forename: Chee Kiat
authors.initials: CK
authors.lastname: Tan
authors.forename: Han Chong
authors.initials: HC
authors.lastname: Toh
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis*; D018932:Chemokine CCL2 / Q000097:blood*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007214:Indonesia; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis*; D011388:Prolactin / Q000097:blood*; D040901:Proteomics; D012372:ROC Curve; D012846:Singapore
chemical_list: D014408:Biomarkers, Tumor; D018932:Chemokine CCL2; D011388:Prolactin