A reduced expression of MMP-9 and MMP-2 in Huh-7 cells, further supporting the notion that in liver cancer, AFP not only contributes to angiogenesis, but may also play a role in tumor invasion. Previous studies by others have demonstrated that AFP itself may stimulate angiogenesis and induce metastasis of liver cancer. Increased serum AFP concentration was correlated with an enhanced VEGF-A Loganin protein expression in HCC tissue. At present, radical surgical resection, chemotherapy or radiation are used as curative treatments for BTC that is diagnosed in early stages. However, this disease is usually fatal, with most patients diagnosed in advanced stages. Therefore, it is imperative to find effective biomarkers for early diagnosis and to elucidate the molecular mechanisms associated with pathogenesis. The Wnt signaling pathway plays an important role in embryonic development, cell differentiation and cell proliferation, and its role in bile duct development has been established. Wnt proteins are secreted molecules that interact with transmembrane receptors of the frizzled family. b-catenin is the most important component of the Wnt signaling pathway, with its altered localization serving as a marker of pathway activation. Once the Wnt ligand binds to its receptor, a complex signaling cascade is activated that leads to stabilization of cytosolic bcatenin. The b-catenin then pools and translocates to the nucleus, where it interacts with LEF/TCF transcription factor, Anemarsaponin-BIII leading to the activation of downstream target genes, including several oncogenes, such as c-myc, cyclin D1 and c-jun. Recently, the aberrant activation of the Wnt signal transduction pathway has been shown to be closely linked to tumorigenesis in adults. Secreted frizzled-related protein-1 is an antagonist of the Wnt signaling pathway that maps to chromosome 8p12-p11.1. SFRP1 harbors a domain that is homologous to the frizzled receptors and can bind Wnt proteins in the extracellular compartment, thus inhibiting ligand�Creceptor interaction and signal transduction. Inactivation of SFRP1 has been reported in a wide range of human malignancies, including ovarian, bladder, mesothelioma, breast, esophageal, prostate and gastric cancers. Furthermore the SFRP1 gene displays a high methylation frequency in cholangiocarcinoma, suggesting the possibility of its tumor-specific inactivation. However, to our knowledge, the role of SFRP1 expression in human biliary tract carcinoma has not been directly examined. The purpose of this study was to examine SFRP1 and b-catenin expression in human BTC by immunohistochemistry. We evaluated the relationship of their expression with clinicopathologic parameters. Our results suggest that SFRP1 may serve as a candidate tumor suppressor gene for BTC. BTC is a rapidly progressive disease with a poor prognosis and an emerging trend of increased 
incidence. Patients with BTC have no obvious early symptoms due to its anatomical and physiological characteristics and therefore are usually diagnosed at an advanced stage. Though advances have been made in the understanding of BTC, the treatment of this lethal disease is still unsatisfactory. Thus, finding prognostic indicators is important both to improve early diagnosis and to ameliorate the prognosis for BTC.