儿童肾母细胞瘤HMGB1、RAGE及VEGF的表达及意义

目的 探讨高迁移率族蛋白-1(HMGB1)、晚期糖基化终末产物受体(RAGE)和血管内皮生长因子(VEGF)在小儿肾母细胞瘤组织中的表达及其在肿瘤血管浸润、淋巴结转移中的意义.方法 收集郑州大学第一附属医院2003年1月至2010年1月小儿外科手术切除经病理证实为肾母细胞瘤的石蜡标本50例、15例同期相应瘤旁组织和7例正常肾组织标本.应用免疫组织化学SP染色辅以计算机图像分析系统分析结果的方法,研究HMGB1、RAGE及VEGF在各组标本中的表达及意义.结果 HMGB1、RAGE在肾母细胞瘤组织中的表达(144.46±13.55、138.18±12.26)与两者在瘤旁组织和正常肾组织中表达(107.47±5.27、103.91±4.29;100.98±4.82、100.82±3.32)相比差异均有统计学意义(P＜0.05),HMGB1在瘤旁与正常肾之间表达差异有统计学意义(P＜0.05).VEGF在瘤体组与瘤旁组中(147.57±13.77,140.28±7.85)和在正常肾组织组中的表达(106.38±1.92)相比差异显著(P＜0.05).三者在临床分期Ⅲ～Ⅳ期和预后不良组织型组及淋巴结转移组的肾母细胞瘤组织中的表达(148.69±12.17、147.73±6.71、163.14±7.50;157.88±4.44、155.29±3.97、169.17±4.42;152.11±7.36、151.56±5.46、163.83±7.20)显著高于临床分期Ⅰ～Ⅱ期和预后良好组织型及无淋巴结转移组(P＜0.05)(139.23±5.83、133.30±11.23、140.85±8.87;139.52±5.22、135.39±9.71、143.94±10.39;138.61±5.59、133.00±8.75、141.18±8.95).相关分析显示肾母细胞瘤组织中HMGB1与RAGE、VEGF的表达均成正相关(r=0.424,P=0.002;r=0.453,P=0.001),RAGE与VEGF之间无明显相关(r=0.237,P=0.101).结论 HMGB1、RAGE和VEGF的高表达与肾母细胞瘤的临床分期、病理类型、淋巴结转移有关,参与了肿瘤血管浸润及淋巴结转移,HMGB1/RAGE可能是促进肾母细胞瘤转移的一条信号通路,给我们靶向治疗肾母细胞瘤提供了新的思路.

Abstract：

Objective This study aim to assess the expressions of high mobility group box chromosomal proteinl ( HMGB1) and receptor foradvanced glycation end products (RAGE) and vascular endothelial growth factor (VEGF) in Wilms'tumor and their clinical significance both in the tumor blood vessel infiltrates and in the lymph node metastasis. Methods Fifty cases of Wilms'tumor samples, which had been confirmed by pathology, were collected from The First Affiliated Hospitals of Zhengzhou University from january 2003 to january 2010. And 15 cases were taken from the adjacent kidney tissues at the same time. Other 7 cases were normal kidney tissues. The expression of HMGB1, RAGE and VEGF were detected by the Immunohistochemical SP staining in each group of specimens. The expression intensity was analyzed by computer image processing and their significance in each group of specimens were studied. Results The expressions of HMGB1 and RAGE in the Wilms'tumor tissues (144. 46 ± 13. 55、138.18 ±12. 26) were compared with those in the adjacent kidney tissues and in the normal kidney tissues( 107. 47 ± 5. 27、103. 91 ± 4. 29; 100. 98 ± 4. 82、 100. 82 ± 3. 32). The expressions of HMGB1 in the adjacent kidney tissues and in the normal kidney showed significant differences. There was a significant differences between the Wilms' tumor group and the adjacent kidney tissues or in the normal kidney tissues ( F ＜ 0.05 ). The expressions of VEGF proteins in Wilms'tumor tissues and in the adjacent kidney tissuess(147. 57 ± 13. 77,140. 28 ± 7. 85) comoared to those in the normal kidnev tissues(106. 38 ± 1. 92)were remarkably different(P＜0. 05). The expressions of HMGB1 ,RAGE and VEGF proteins in Wilms' tumor tissues of stage Ⅲ-Ⅳ and high risk histopathology and lymph node metastasis group (148. 69 ± 12.17、147. 73 ± 6. 71、163.14 ± 7. 50; 157. 88 ± 4. 44、155. 29 ± 3. 97、169. 17±4.42;152. 11 ± 7. 36、151. 56 ± 5. 46、163. 83 ± 7. 20)were significantly higher than those of stage Ⅰ-Ⅱ and low risk histopathology and no lymph node metastasis group(P＜0. 05) (139. 23 ± 5. 83、133. 30 ± 11. 23、140. 85 ± 8. 87; 139. 52 ± 5. 22、135. 39 ± 9. 71、143. 94 ± 10. 39; 138. 61 ± 5. 59、133. 00 ±8. 75、141.18 ± 8. 95). There was a positive correlation between the expressions of HMGB1 with RAGE and VEGF(r = 0. 424, P = 0. 002; r = 0. 453, P = 0. 001), but the correlation between the RAGE and VEGF is not clear (r = 0. 237, P = 0. 101). Conclusions There was a high expression of HMGB1 ,RAGE and VEGF in the Wilms'tumor tissues and they are partly related to the clinical stages and pathological type and lymph node metastasis of Wilms'tumor. They perhaps participated in the tumor blood vessel infiltration and the lymph node metastasis and the pathway of HMGB1/RAGE is perhaps the main mechanism correlated with the metastasis of Wilms'tumor.

The expression and significance of HMGB1, RAGE and VEGF in Wilms' tumor

Objective This study aim to assess the expressions of high mobility group box chromosomal proteinl ( HMGB1) and receptor foradvanced glycation end products (RAGE) and vascular endothelial growth factor (VEGF) in Wilms'tumor and their clinical significance both in the tumor blood vessel infiltrates and in the lymph node metastasis. Methods Fifty cases of Wilms'tumor samples, which had been confirmed by pathology, were collected from The First Affiliated Hospitals of Zhengzhou University from january 2003 to january 2010. And 15 cases were taken from the adjacent kidney tissues at the same time. Other 7 cases were normal kidney tissues. The expression of HMGB1, RAGE and VEGF were detected by the Immunohistochemical SP staining in each group of specimens. The expression intensity was analyzed by computer image processing and their significance in each group of specimens were studied. Results The expressions of HMGB1 and RAGE in the Wilms'tumor tissues (144. 46 ± 13. 55、138.18 ±12. 26) were compared with those in the adjacent kidney tissues and in the normal kidney tissues( 107. 47 ± 5. 27、103. 91 ± 4. 29; 100. 98 ± 4. 82、 100. 82 ± 3. 32). The expressions of HMGB1 in the adjacent kidney tissues and in the normal kidney showed significant differences. There was a significant differences between the Wilms' tumor group and the adjacent kidney tissues or in the normal kidney tissues ( F ＜ 0.05 ). The expressions of VEGF proteins in Wilms'tumor tissues and in the adjacent kidney tissuess(147. 57 ± 13. 77,140. 28 ± 7. 85) comoared to those in the normal kidnev tissues(106. 38 ± 1. 92)were remarkably different(P＜0. 05). The expressions of HMGB1 ,RAGE and VEGF proteins in Wilms' tumor tissues of stage Ⅲ-Ⅳ and high risk histopathology and lymph node metastasis group (148. 69 ± 12.17、147. 73 ± 6. 71、163.14 ± 7. 50; 157. 88 ± 4. 44、155. 29 ± 3. 97、169. 17±4.42;152. 11 ± 7. 36、151. 56 ± 5. 46、163. 83 ± 7. 20)were significantly higher than those of stage Ⅰ-Ⅱ and low risk histopathology and no lymph node metastasis group(P＜0. 05) (139. 23 ± 5. 83、133. 30 ± 11. 23、140. 85 ± 8. 87; 139. 52 ± 5. 22、135. 39 ± 9. 71、143. 94 ± 10. 39; 138. 61 ± 5. 59、133. 00 ±8. 75、141.18 ± 8. 95). There was a positive correlation between the expressions of HMGB1 with RAGE and VEGF(r = 0. 424, P = 0. 002; r = 0. 453, P = 0. 001), but the correlation between the RAGE and VEGF is not clear (r = 0. 237, P = 0. 101). Conclusions There was a high expression of HMGB1 ,RAGE and VEGF in the Wilms'tumor tissues and they are partly related to the clinical stages and pathological type and lymph node metastasis of Wilms'tumor. They perhaps participated in the tumor blood vessel infiltration and the lymph node metastasis and the pathway of HMGB1/RAGE is perhaps the main mechanism correlated with the metastasis of Wilms'tumor.