Expression And Clinical Feature Of UPAR MRNA In The Peripheral Blood Of Esophageal Cancer Patients

uPA is a central molecule in pericellular proteolysis. It converts enzymatically inactive plasminogen into the widely acting serine protease plasmin. The urokinase plasminogen activator (uPA) system represents a family of serine proteases that are involved in the degradation of basement membrane and the extracellular matrix, leading to tumor cell invasion and metastasis. After binding with uPA, uPAR serves many known functions, including:cell movement and adhesion through extracellular matrix degradation; stimulation of the diacylglycerol pathway; discharging internally stored calcium; and interacting with integrins. Although emerging evidence suggests that uPARmRNA is causally involved in cancer formation and progression, little is known about its significance in peripheral blood about esophageal squamous cell cancer. In the present study, the expression of uPARmRNA in peripheral blood was analyzed to explore the relationship between the uPAR mRNA expression and the infiltration and metastasis factors in the esophageal squamous cell carcinoma.PartⅠExpression of uPAR mRNA in the peripheral blood of esophageal squamous cell cancer patients.Objective:To explore the relationship between the uPAR mRNA expression in peripheral blood and the esophageal squamous cell carcinoma invasion and metastatic lymph node.Methods We assessed specific uPAR mRNA expression in peripheral blood in 26 specimens of esophageal carcinoma including 17 cases in man and 9 in female. All patients received surgical treatment and no neoadjuvant radiotherapy and chemotherapy befor operation. Their age ranged from 43 to 75 with average age 61.5 years. There was 13 cases inⅡstage and 23 inⅢ. For every patient, the venous blood was taken suction of 5ml in 1d preoperation and 14d postoperation. For normal negative controls, peripheral bloods were collected from 10 volunteer having no malignancy. The specimen was immediately mixed with 4ml of ISOGEN-LS and stored. Total RNA was extracted according to the Trizol manufacturer’s protocols and was gone through reverse transcription and amplification by RT-PCR. After gel electrophoretic analysis, the result was analysed by chemoluminescence imaging system. The uPAR protein was detected in the esophageal squamous cell carcinoma tissue by immunohistochemistry.Results 1、The uPAR protein showed high expression in the esophageal squamous cell carcinoma tissue, discordant with gender,age, family medical history, differentiation and invasion, and concordant with lymph node metastasis and staging of tumor.2、The uPARmRNA in the peripheral blood showed concordant expression with lymph node metastasis and staging of tumor and discordant with gender,age, family medical history, differentiation and invasion, and the difference had statistical significance (P<0.05).3、The difference of the uPARmRNA in the peripheral blood had no statistical significance between 1d preoperation and 14d postoperation. The difference had statistical significance in lymph node metastasis and staging of tumor, which illustrate the expression of uPARmRNA was related with lymphadenectomy.4、The lymph node metastasis and depth of tumors invasion were independent prognostic factor for uPAR expression in peripheral blood by multivariate analysis. The gender,age, family medical history, differentiation and invasion were no independent prognostic factor.Conclusion The expression of uPAR was significantly correlated with the depth of tumors invasion and distant metastasis. And the expression of uPAR in the peripheral blood is a marker for metastasis and tumors invasion. Part II The relationship between the prognosis of esophageal squamous cell cancer cases and expression of uPAR mRNA in peripheral bloodObjective:To explore the relationship between the uPAR mRNA expression in peripheral blood and the prognosis of esophageal squamous cell cancer patients.Methods We assessed specific uPAR mRNA expression in peripheral blood in 19 specimens of esophageal carcinoma including 13 cases in man and 6 in female. All patients received surgical treatment and no neoadjuvant radiotherapy and chemotherapy befor operation. Their age ranged from 42 to 70 with average age 57.3 years. There was 12cases inⅡstage and 7 inⅢ. For every patient, the venous blood was taken suction of 5ml in 1d preoperation and 14d postoperation. For normal negative controls, peripheral bloods were collected from 10 volunteer having no malignancy. The expression of CEA, CEAmRNA和uPARmRNA was detected by RT-PCR and ELISA.Results 1、The average value of CEA density in peripheral blood was 32.8±11.6ng/ml in esophageal squamous cell cancer cases and 3.1±1.4ng/ml in volunteer, and the difference had statistical significance (P<0.05).2、The uPARmRNA in the peripheral blood showed concordant expression with lymph node metastasis and staging of tumor and discordant with gender,age, family medical history, differentiation and invasion. In addition, the distant metastasis and depth of tumors invasion were independent prognostic factor for distant metastasis in peripheral blood by multivariate analysis.3、The overexpression of uPARmRNA was significantly associated with the prognosis and metastasis of esophageal squamous cell tumor and can serve as an independent prognostic factor.Conclusion The expression of uPAR was significantly correlated with the prognosis and metastasis of esophageal squamous cell tumor and can serve as an independent prognostic factor.