Idenifcation of L1CAM as the potential biomarker for HCC metastasis

Abstract

Background The poor prognosis of HCC is commonly associatedwith metastasis and recurrence. Recently, two HCC metastatic celllines MHCC-97L and MHCC-97H, with different metastastic poten-tial, were established. A high density human U133 plus 2.0 cDNAmicroarray was used to examine their genetic alterations. Among theeight most up-regulated genes, we identified L1 adhesion molecule(L1CAM) as a potential important protein for HCC metastasis.Methods and Results In this study, we investigated expressionpatterns of L1CAM in human HCC tumor samples and correlationto clinicopathologic variables including patient survival times. Thefunctional role of L1 was also studied in-vitro. Finally, we alsoassessed whether soluble L1CAM detected in serum samples of HCCpatients L1CAM expression is associated significantly with venousinfiltration (p = 0.001), advanced TNM stage (p < 0.001), recurrence(p < 0.001) and microsatellite formation (p = 0.011). By tissuemicroarray, L1 expression was correlated with HCC metastasis (p <0.05). Strong membranous L1 expression correlated significantly withshorter survival and disease-free survival (p = 0.0129 and p = 0.0046respectively). Consistently, L1 expression was only found in metasta-tic HCC cell lines but not the primary ones. By ectopic L1 cDNAtransfection into Hep3B cell, increased metastatic potential was evi-denced by wound healing assay and invasion assay. L1CAM pro-moted both lung and liver metastases after tail vein injection of nudemice. By immunoprecipitation, we could detect ectodomain of L1 inHCC patients’ serum and their expression was significantly elevatedwhen compared with the normal controls.Conclusion L1CAM is a new marker for prediction of clinicaloutcome and could be helpful to identify patients with HCC who areat high risk for recurrent disease.