Published online Jun 21, 2015. doi: 10.3748/wjg.v21.i23.7254
Peer-review started: December 8, 2014
First decision: January 27, 2015
Revised: February 6, 2015
Accepted: March 19, 2015
Article in press: March 19, 2015
Published online: June 21, 2015
AIM: To determine the cut-off value of intercellular adhesion molecule-1 (ICAM-1) and assess the correlation of ICAM-1 with clinicopathological features and the prognosis of hepatocellular carcinoma (HCC) patients who underwent surgical resection.
METHODS: We prospectively collected clinicopathological data from 236 HCC patients who had undergone successful hepatectomy. Receiver operating characteristic curve analysis was performed to determine the optimal cut-off value of ICAM-1. Enzyme-linked immunosorbent assay was used to measure the concentration of ICAM-1 in 236 serum samples isolated from HCC patients and the stratified analysis was used to compare the serum level of ICAM-1 in different HCC subgroups. Immunohistochemistry was performed to test the expression level of the ICAM-1 protein in 76 cases of HCC tissues and their adjacent normal liver tissues (ANLT). The survival probability of HCC patients was estimated using Kaplan-Meier plots and differences between the groups were obtained using the log-rank test. Furthermore, independent indicators of the prognosis were acquired using a stepwise Cox proportional hazard model to analyze a series of predictors that were associated with disease-free survival (DFS) and overall survival (OS) in HCC patients.
RESULTS: Our findings suggested that ICAM-1 promotes HCC metastasis and high serum ICAM-1 is significantly associated with alpha-fetoprotein (AFP) (P = 0.022), clinical tumor-node-metastasis stage (P < 0.001), portal vein tumor thrombus (P = 0.005), distant metastasis (P = 0.016) and recurrence (P = 0.034). We further detected the ICAM-1 protein in HCC specimens and found that 56 of 76 (73.7%) HCC tissues had ICAM-1 positive staining while only 23 of 76 (30.3%) ANLT were positively stained (P < 0.0001). Survival analysis indicated that HCC patients with increased ICAM-1 concentrations had significantly shorter DFS and OS after resection. A multivariate analysis showed that ICAM-1 > 684 ng/mL was an independent factor for DFS (HR = 1.643; 95%CI: 1.125-2.401; P = 0.010) and OS (HR = 1.692; 95%CI: 1.152-2.486; P = 0.007).
CONCLUSION: ICAM-1 may be a promising serological biomarker for HCC diagnosis and an independent predictor of DFS and OS after surgical resection and may provide a useful reference for the prediction of intra- and extrahepatic metastasis.
Core tip: Our previous research and other studies found that intercellular adhesion molecule-1 (ICAM-1) is overexpressed in hepatocellular carcinoma (HCC) and might be a biomarker for HCC diagnosis. However, the correlation between ICAM-1 and clinicopathological features and its prognostic significance for HCC have not been explored. In this paper, we validate that ICAM-1 promotes HCC metastasis and that high serum ICAM-1 is significantly associated with alpha-fetoprotein, clinical tumor-node-metastasis stage, portal vein tumor thrombus, distant metastasis, recurrence, disease-free survival and overall survival. ICAM-1 may be a promising serological biomarker for HCC diagnosis and prognosis and may provide a useful reference for the prediction of intra- and extrahepatic metastasis.