| Objective: This study was designed to detect the level of VEGF-C,VEGF-D and VEGFR-3 of serum in patients with Nasopharyngeal Carcinoma(NPC), and investigate the relationship between circulating level of VEGF-C,VEGF-D and VEGFR-3 and clinical parameters and state of metastasis to lymphatic node in patients with nasopharyngeal carcinoma. To assess the diagnostic utility of circulating level of VEGF-C,VEGF-D and VEGFR-3 and the combination assay of these factors in predicting lymph node metastasis in Nasopharyngeal Carcinoma patients.Methods:CNE-2 cell cultured supernatants was measured by ELISA and sVEGF-C,sVEGF-D and sVEGFR-3 levels were evaluated to determine the relationship between them and number of cells. The soluble form of VEGF-C,VEGF-D and VEGFR-3 levels in sera of 29 initial NPC patients,7 relapsed NPC patients,13 complete remission patients,15 NPC patients with distant metastasis, and 15 healthy controls were quantitatively measured by ELISA in comparison with the relationship between and clinical characters and between TNM stage. Logistic regression models and ROC curves were used to analyze the influence of VEGF-C, VEGF-D and VEGFR-3 and the combination assay of these factors on the probability of presence or absence of lymph node metastasis.Results:1.The concentration of VEGF-C in 1×105/ml,5×105/ml and 1×106/ml CNE-2 cell cultured supernatants was (167.58±0.35)pg/ml, (192.98±1.14)pg/ml and (227.59±13.23) pg/ml respectively.The VEGF-D was (514.18±6.96)pg/ml,(625.54±72.53)pg/ml, (793.98±18.96) pg/ml respectively. The VEGFR-3 was (682.71±45.27)pg/ml, (1386.99±181.09)pg/ml, (1915,21±113.18)pg/ml respectively.There was linear correlation between the concentration of VEGF-C, VEGF-D and VEGFR-3 and the count of CNE-2 cells cultured(r=0.976,r=0.966,r=0.974,P=0.001,P=0.002,P=0.001).2.(1)Serum levels of VEGF-C,VEGF-D and VEGFR-3 in initial NPC patients,in relapsed NPC patients,and metastasis patients were significantly higher than those in healthy controls[(226.84±36.47) pg/ml, (238.99±20.41)pg/ml, (259.44±38.40)pg/ml,vs. (98.70±46.10) pg/ml,P=0.000 respectively] and significantly higher than those in complete remission(CR) patients (148.4±33.33) pg/ml, (P=0.000 respectively).Serum levels of VEGF-C and VEGF-D in CR patients were significantly higher than those in healthy controls[(228.05±85.31pg/ml)pg/ml vs. (174.56±59.54)pg/ml,P=0.011].There was no significance of serum level of VEGFR-3 between CR and healthy controls[(681.48±335.72)pg/ml)pg/mlvs.(747.81±385.0pg/ml),P=1.000].(3)Seru m levels of VEGF-C,VEGF-D and VEGFR-3 in T3-T4 stage and N1-N3 stage patients was significantly higher than those in T1-T2 and NO stage patients(P<0.05 respectively).There was correlation between the TNM stage and the serum levels of VEGF-C,VEGF-D and VEGFR-3 (r=0.568,r=0.660,r=0.438,P=0.000 respectively).The area under the ROC curve of detecting VEGF-C/VEGF-D and VEGFR-3 singly is 0.913,0.768 and 0.815 respectively. The area under the ROC curve of detecting VEGF-C and VEGF-D combined,VEGF-C and VEGFR-3 combined,VEGF-D and VEGFR-3 combined and VEGF-C,VEGF-D and VEGFR-3 combined is 0.920,0.942,0.906 and 0.957. Conclusions:It is suggested that there is correlation between the development of Nasopharyngeal carcinoma and levels of sVEGF-C,sVEGF-D and sVEGFR-3 in sera of NPC patients. The concentration of sVEGF-C,sVEGF-D and sVEGFR-3 could be used as index to determine whether patient's condition have been advanced. Combined detecting of VEGF-C, VEGF-D and VEGFR-3 in circulation could be a index to determine whether there is lymph node metastasis in NPC patients. |
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