Thrombin light chain and GRO-1 as potential serum biomarkers and their relationship with clinicopathological features of hepatocellular carcinoma

Abstract

Objective To identify potential serum biomarkers specific for hepatocellular carcinoma (HCC).Methods Eighty-one patients wilh hepatitis B-related HCC and 80 healthy controls were randomly divided into a training set (48 HCC,47 controls) and a testing set (33 HCC,33 controls).Serum proteomic profiles were measured using surface-enhanced laser desorption/ionization time-offlight mass spectroscopy (SELDI-TOF-MS).A classification tree was established by the Biomarker Pattern Software.Candidate biomarkcrs were separated by HPLC and identified by MA1DI-MS/MS and database searching.Forty-eight patients with HCC,54 cirrhotic patients and 42 healthy subjects were clinically validated using candidate biomarkers by SELDI-Immunoassay.Real-time reverse transcriptase-polymerase chain reaction was performed to observe GRO-1 and Thrombin in 55 HCC tissues and 13 normal hepatolage tissues.Results Two up-regulated protein peaks were automatically chosen as a classification tree in the training set.These biomarkers were identified as thrombin light chain and CXC chemokines ligand 1 (GRO-1).The sensitivity and specificity of this classification tree were 89.6％.The multivariate model using the two biomarkers and alpha-fetoprotein (AFP) resulted in a sensitivity of 91.7％ and specificity of 92.7％,which was significantly better than AFP alone.The mRNA expression of GRO-1 and Thrombin were found in all HCC tissues.There were significant associations between GRO-1 gene expression and some clinical and pathological findings such as metastasis and recurrence (P＜0.05).Significant differences of 5-year survival rates wee observed among subgroups according to the expression of GRO-1 (P＜0.05).There were significant associations between Thrombin gene expression and some clinical and pathological findings such as recurrence and AFP (P＜0.05).Significant differences of 5-year survival rates were observed among the subgroups according to the expression of THROMBIN (P＜0.05).A positive correlation was found between GRO-1 and Thrombin (r=0.73,P＜0.01).Conclusion Thrombin light chain and GRO-1 are potential biomarkers of HCC.The expression of GRO-1 in HCC tissues was a valuable indicator in estimating metastasis and recurrence in HCC patients. Key words: Hepatocellular carcinoma; Biomarker; Growth-regulated oncogane; Thrombin; Prognosis