Identification of serum CCL15 in hepatocellular carcinoma

Background: Early serum detection is of critical importance to improve the therapy for hepatocellular carcinoma (HCC), one of the most deadly cancers. Hepatitis infection is a leading cause of HCC. Methods: In the present study, we collected total serum samples with informed consent from 80 HCC patients with HBV (+)/cirrhosis (+), 80 patients with benign diseases (50 liver cirrhosis patients and 30 HBV-infected patients) and 60 healthy controls. Analysis was by using surface-enhanced laser desorption/ionisation-time-of-flight mass spectroscopy (SELDI-TOF-MS) to find new serum markers of HCC. SELDI peaks were isolated by SDS-PAGE, identified by LC-MS/MS and validated by immunohistochemistry (IHC) in liver tissues. Migration and invasion assay were performed to test the ability of cell migration and invasion in vitro. Results: SELDI-TOF-MS revealed a band at 7777 M/Z in the serum samples from HCC patients but not from healthy controls or patients with benign diseases. The protein (7777.27 M/Z) in the proteomic signature was identified as C-C motif chemokine 15 (CCL15) by peptide mass fingerprinting. A significant increase in serum CCL15 was detected in HCC patients. Functional analysis showed that HCC cell expressed CCL15, which in turn promoted HCC cell migration and invasion. Conclusion: CCL15 may be a specific proteomic biomarker of HCC, which has an important role in tumorigenesis and tumour invasion.