The Expression And Clinical Significance Of LOX And VEGF In Hepatocellular Carcinoma

Objective: The hepatocellular carcinoma (HCC) is one of the most common malignant tumors in our country with the second annual mortality. Its has a low excisional rat and a poor prognosis. Lysyl oxidase(LOX) is a copper-dependent amine oxidase that is secreted out of cells to initiate the covalent cross-linking of collagens and elastin in extracellular matrices (ECM). The production and activity of LOX can ensure the integrity of ECM structure. Studies have showed the down-regulation and even lack of LOX in various tumor tissues or transformed cells and have demonstrated the intracellular roles of LOX recently, including transcription regulation, cellular motoricity/migration and cell adhesion. And LOX can facilitate metastasis and invasion of breast cancer cell. But the relationship between LOX and the invasion of tumor is still not certain.HCC is a typical multivessel tumor with vigorous grouth and quite easily to have intrahepatic vessel infiltration and form tumor embolus. And therapeutic effect of HCC is quite unsatisfactive. In most of tumor, vascular endothelial growth factor(VEGF) has an up-regulation and can obviously induce tumor vascularization to facilitate tumor growth and metastasis. The expression of VEGF is obviously up-regulated in HCC and correlate closely with tumor size, embolus formation and TNM staging. The patients with VEGF expression usually have a poor prognosis.Up to now, we still not see any report about the detection combined LOX with VEGF in HCC at home and abroad. In this experiment, immunohistochemistry was used to detect the protein expression of LOX and VEGF in HCC, para-cancerous tissues and normal hepatic tissues. Our destination is to find out the role LOX has played in HCC occurrence, development, invasion and vascularization and the relationship between LOX and VEGF. By this experiment, we hope to find out a new way to reveal the invasive mechanism of the HCC.Methods: Sixty one tumor tissue samples and thirty six para-cancerous tissue samples were obtained from the primary HCC patients undergoing surgical resection. Nineteen normal hepatic tissue samples were taken from the patients with benign tumor. Immunohistochemistry was used to detect the protein expression of LOX and VEGF in HCC, para-cancerous tissues and normal hepatic tissues. Statistical analysis was used to analyze the different expression intensity of LOX in these tissues, the relationship between LOX and VEGF and the correlation between LOX and clinical pathological parameters.Results:1 LOX positive stain was observed in thirty-six of 61 tumor tissue samples (59.0%), thirty-two of 36 para-cancerous tissue samples (88.9%) and eighteen of 19 normal liver tissue samples (94.7%). The expression of LOX in HCC was significantly lower than that in para-cancerous tissues and normal liver tissues(P<0.01).2 The expression of LOX in HCC were significantly lower when tumor had low differentiation, more piece numbers, surrounding invasion and distant metastasis and higher in the samples with hepatic fibrosis and viral hepatitis type B ro C (P<0.05). The expression of LOX didn't correlate with age, gender, tumor size, tumor embolus, intrahepatic or lymphatic metastasis, AFP and Ferritin.3 VEGF positive stain was observed in forty-seven of 61 tumor tissue samples (77.0%), twenty-six of 36 para-cancerous tissue samples (72.2%) and four of 19 normal liver tissue samples (20.1%). The expression of VEGF in HCC is significantly higher than that in para-cancerous tissues and normal liver tissues(P<0.01).4 The expression of VEGF in HCC were observed significantly higher when tumor had embolus, intrahepatic or lymphatic metastasis (P<0.05). The expression of LOX didn't correlate with tumor size, numbers, differentiation, surrounding invasion and distant metastasis.5 LOX had a positive correlation with VEGF in HCC (P<0.05).Conclusions:1 LOX had a low expression in HCC. Its expression down-regulated signaficantly with the poor differentiation, more tumor numbers, surrounding invasion and distant metastasis. These indicated that LOX may be relevant to the invasion and the metastasis of HCC.2 The down-regulation of LOX accompanied with the up-regulation of VEGF can promote the growth and invasion of HCC.