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.

Evaluation of Taline-1, MCP-1 and IGF-1 in Prediction the Risk of Developing Hepatocellular Carcinoma in Patients With Liver Cirrhosis

“…The results are similar to that of Wang et al, (19) who found that serum MCP-1 levels were significantly higher in the HCC group than in the cirrhotic group or the controls. However, our rsults revealed that no statistical significant difference was found between patints with liver cirrhosis and the (20) found that there was a significant increase in level of MCP-1 in patients with all grades of hepatic affection in comparison to controls.…”

“…No correlations were found between the studied marker and the other parameters. Wang et al, (19) found no significant correlation between MCP-1 and liver function tests. ROC curve analysis revealed that at a cutoff level of 52.0 ng/ml, MCP-1 can discriminate between HCC and cirrhotic patients with a sensitivity of 100 % which was higher than both AFP and taline-1.…”

The insulin-like growth factor 2 (IGF2) mRNA-binding protein p62/IGF2BP2-2 as a promoter of NAFLD and HCC?

“…In fact, recent data also suggested a potential role for MCP-1 in HCC. 9 We suggest that p62 might also drive the progression from NAFLD towards HCC. Interestingly, p62 induces or amplifies several of the most important mechanistic links between NAFLD and HCC as highlighted by Stickel and Hellerbrand.…”

–2518 A/G MCP-1 but not –403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma

“…Tsaur et al [28] reported down-regulation of MCP-1 and gene expression of other chemokines in renal cell cancer. In contrast, chemokine over-expression was reported in some other cancers [29–31]. The nature of MCP-1 involvement in oncologic disorders is still unknown.…”