The Clinical Significance Of Detecting Plasma VEGF Concentration In Non-hodgkin's Lymphoma

Objective : Many studies discover the growth and metastasis of cancer are closely associated with the formation of tumors blood vessels Vascular endothelial growth factor (VEGF) is the strongest growth factor to stimulate angiogenesis. There is overexpression of VEGF in many human malignant tumors, including NHL. In this study ELISA was used to detect the plasma VEGF (P-VEGF) of the NHL patients on different disease stage. And it also used to investigate the P-VEGF concentration change between pre-treatment and post-treatment of NHL patients himself. Hoping to find the relationship between P-VEGF concentration and clinical condition. Hoping to explore the predictive value of P-VEGF on chemotherapy response and therapeutic efficacy in newly diagnosed NHLs. We also researched the relationship between the P-VEGF level and the clinicolpathological factors. To study non-hodgkin's lymphoma from angiogenesis so as to have a new strategy for the treatment of non-Hodgkin's lymphoma and to observe clinical condition in NHL patients. Methods: We quanitated the plasma VEGF on different disease stage of NHL patients by ELISA. P-VEGF on pre-treatment and on post-treatment was also detectes by ELISA; collecet relative clinical material and analyze the ralationship between these data and predictive value of P-VEGF on chemotherapy response and therapeutic efficacy in newly diagnosed NHLs or the clinicopathological factors. Results: 1. The plasma VEGF concentration of the untreated NHL patients ranged grom 11.4 to 388.6 pg/ml; median 170.2 pg /ml. The plasma VEGF concentration of the normal controls ranged grom 11.4 to 119.1 pg/ml; median 63.6 pg/ml. The plasma VEGF of the untreated NHL group was significantly higher than that of the control (p<0.05). 2. The plasma VEGF concentration of the untreated NHL patients ranged from 11.4 to 388.6 pg/ml; median 170.2 pg/ml. The plasma VEGF concentration of patients in complete remission (CR) ranged from 20.5 to 119.1 pg/ml; median 40.9 pg/ml. The plasma VEGF concentration of patients in partial remission (PR) ranged from 63.6 to 172.3 pg/ml; median 106.4 pg/ml. The plasma VEGF concentration of patients with progressive disease (PD) ranged from 54.5 to 388.6 pg/ml; median 231.4 pg/ml. The plasma VEGF concentration of the untreated NHL patients was significantly higher than that of patients in CR (p<0.05) and was also higher than that of patients in PR,but no significance between the patients in PR and the untreated NHL patients (p>0.05). The plasma VEGF concentration of the patients with PD was increased , which was was significantly higher than that of patients in CR (p<0.05), but no significance between the patients with PD andthe untreated NHL patients (p>0.05). No significance between the plasma VEGF of CR patients and the plasma VEGF of the normal controls was found (p>0.05). No significance between the plasma VEGF of PR patients and the plasma VEGF of the normal controls was found (p>0.05). The plasma VEGF concentration of the patients with PD was significantly higher than that of the controls (p<0.05). 3. The pre-treatment and post-treatment plasma VEGF in the patients of himself who received first CR after treatment were also detected by ELISA. The pre-treatment plasma VEGF in the patients who received first CR ranged from 11.4 to 362.9 pg/ml; median 170.2 pg/ml. The post-treatment plasma VEGF in the patients who received first CR ranged from 20.5 to 172.3 pg/ml; median 63.6 pg/ml. The high plasma level of VEGF has a tendency to drop after receiving CR. And there was statistical significance between the pre-treatment and the post-treatment plasma VEGF in the patients of himself who received first CR (p<0.05). No significance between the post-treatment plasma VEGF and the plasma VEGF of the normal controls was found (p>0.05). When the diease was progressing, the plasma VEGF was detected again. The plasma level of VEGF of the patients with PD ranged from 54.5 to 388.6 pg/ml; median 231.4 pg/ml. The plasma level of VEGF with PD was increased, which was significantly higher than that of himself in CR (p<0.05), and was also a little higher than that of himself in untreated (p<0.05), but no significance was found (p>0.05).4. The plasma VEGF concentration of untreated patients who received CR after the first chemo-therapy ranged from 11.4 to 180.9 pg/ml; median 100 pg/ml. The plasma VEGF concentration of untreated patients who didn't receive CR after the first chemo-therapy ranged from 140.4 to 388.6 pg/ml; median 214.65 pg/ml. There was significance between the two groups (p<0.05). 5. Among the 21 NHL untreated patients whose P-VEGF was higher than the median value (170.2 pg/ml), there were 7 patients who received CR after the first chemo-therapy but there were 14 patients who didn't received CR after the first chemo-therapy. Patients with higher than the median P-VEGF had a 33.33% CR rate. Among the 22 NHL untreated patients whose P-VEGF was lower than the median value (170.2 pg/ml), there were 17 patients who received CR after the first chemo-therapy but there were 5 patients who didn't received CR after the first chemo-therapy. Patients with lower than the median P-VEGF had a 77.27% CR rate. There was significance between the two rates (p<0.05). All patients had been followed-up for 6 cycles chemo-therapy. Among the 21 NHL untreated patients whose P-VEGF was higher than the median value (170.2 pg/ml), there were 6 patients who was still in CR but there were 15 patients who wasn't still in CR. Patients with higher than the median P-VEGF had a 28.57% CR rate. Among the 22 NHL untreated patients whose P-VEGF was lower than the median value (170.2 pg/ml), there were 18patients who was still in CR but there were 4 patients who wasn't still in CR. Patients with lower than the median P-VEGF had a 81.82% CR rate. There was significance between the two rates, respectively (p<0.05). 6. If the median P-VEGF concentration was used as the cut-off value, a high P-VEGF was strongly associated with a higher than the normal serum lactate dehydrogenase (S-LDH) level (p<0.05), but no association beween P-VEGF and age at diagnosis, gender, Ann Arbor stage, the presence of B-symptoms, No. of extranodal sites, a higher histological grade or immuno-classification (T-cell or B-cell) was found (p>0.05). 7. There was linear correlation between the plasma VEGF concentration of the untreated patients and the serum lactate dehydrogenase (S-LDH) concentration (p<0.05), but no association beween P-VEGF and β2-microglobulin or erythrocyte sedimentation rate (ESR) was found (p>0.05). Conclusion: 1. The plasma VEGF of the untreated NHL group was significantly higher than that of the control (p<0.05). 2. The plasma VEGF concentration of the untreated NHL patients and of PD patients was not only significantly higher than that of patients in CR respectively (p<0.05), but also higher than that of patients in PR, but no significance between the patients in PR and the untreated NHL patients or PD patients, respectively (p>0.05). The plasma VEGFconcentration of PD patients was higher than that of the untreated NHL patients, but no significance between the PD patients and the untreated NHL patients was found (p>0.05). No significance between the plasma VEGF of CR patients and the plasma VEGF of the normal controls was found (p>0.05). No significance between the plasma VEGF of PR patients and the plasma VEGF of the normal controls was found (p>0.05). The plasma VEGF concentration of the patients with PD was significantly higher than that of the controls (p<0.05). 3. The high plasma level of VEGF has a tendency to drop after receiving CR by treatment. No significance between the post-treatment plasma VEGF and the plasma VEGF of the normal controls was found (p>0.05). When the diease was progressing, the plasma VEGF increased again. 4. The plasma VEGF concentration of untreated patients who received CR after the first chemo-therapy was lower than that of the untreated patients who didn't receive CR after the first chemo-therapy. There was significance between the two groups (p<0.05). Patients with lower than the median P-VEGF had a higher treatment response. 5. The plasma VEGF level of untreated patients was associated with the newly therapeutic efficacy in patients who received CHOP chemotherapy. The CR rate in patients with lower level of P-VEGF was significantly higher than that in patients with higher level of P-VEGF. There was significance between the two rates (p<0.05).