血清NRP-1在早期非小细胞肺癌中的表达及意义
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摘要
目的检测血清神经纤毛蛋白1(NRP-1)在早期非小细胞肺癌(NSCLC)中的表达及意义。方法收集80例新确诊但未经治疗的NSCLC患者、40例健康对照组及20例术后对照组患者的资料,采用酶联免疫吸附试验(ELISA)法检测NSCLC组、健康对照组及术后对照组的血清NRP-1水平,判断其能否作为早期NSCLC的血清学诊断指标,并分析血清NRP-1水平与NSCLC患者各项临床病理参数之间的关系,探索其在NSCLC发展中的作用。结果 NSCLC组血清NRP-1水平显著高于健康对照组及术后对照组(P<0.05)。血清NRP-1水平作为NSCLC生物标志物的ROC曲线下面积为0.73,敏感度为75.0%,特异度为75.0%,95%CI为0.544～0.819(P<0.05)。血清NRP-1水平与NSCLC患者的TNM分期及淋巴结转移显著相关(P<0.05),而与患者的年龄、性别、肿瘤最大直径、病理类型及病理分级无关(P>0.05)。结论 NRP-1有望成为早期NSCLC的血清学诊断指标,且对是否发生淋巴结转移有较好的预测价值。
Objective To evaluate the diagnostic value of the expression of Neuropilin-1(NRP-1) in serum of non-small cell lung cancer(NSCLC) and normal people. Methods The data of 80 NSCLC patients who had been newly diagnosed and previously untreated were collected. Another 20 NSCLC patients after operation were selected as post-operative control group and 40 healthy people were taken as the normal control group. The expression of NRP-1 proteins in the serum was detected by ELISA. Analyze the association between its expression and the clinicopathological characteristics of NSCLC patients. Results The levels of NRP-1 in serum of NSCLC group were significantly higher than those of the normal group and post-operative group(P<0.05). The area under ROC curve of serum NRP-1 level as a biomarker of NSCLC was 0.73, the sensitivity was 75.0%, and the specificity was 75.0%, and the 95% CI was 0.544～0.819(P<0.05). The expression of serum NRP-1 was significantly correlated with TNM stage and the presence or absence of lymph node metastasis(P<0.05), but not with the age, gender, maximum tumor diameter, pathological type and grade(P>0.05). Conclusion NRP-1 is expected to be a serological diagnostic index for early non-small cell lung cancer, and it has a good predictive value for vascular metastasis.
Objective To evaluate the diagnostic value of the expression of Neuropilin-1(NRP-1) in serum of non-small cell lung cancer(NSCLC) and normal people. Methods The data of 80 NSCLC patients who had been newly diagnosed and previously untreated were collected. Another 20 NSCLC patients after operation were selected as post-operative control group and 40 healthy people were taken as the normal control group. The expression of NRP-1 proteins in the serum was detected by ELISA. Analyze the association between its expression and the clinicopathological characteristics of NSCLC patients. Results The levels of NRP-1 in serum of NSCLC group were significantly higher than those of the normal group and post-operative group(P<0.05). The area under ROC curve of serum NRP-1 level as a biomarker of NSCLC was 0.73, the sensitivity was 75.0%, and the specificity was 75.0%, and the 95% CI was 0.544～0.819(P<0.05). The expression of serum NRP-1 was significantly correlated with TNM stage and the presence or absence of lymph node metastasis(P<0.05), but not with the age, gender, maximum tumor diameter, pathological type and grade(P>0.05). Conclusion NRP-1 is expected to be a serological diagnostic index for early non-small cell lung cancer, and it has a good predictive value for vascular metastasis.
引文
[1]Torre LA, Siegel RL, Jemal A. Lung Cancer Statistics[J].Adv Exp Med Biol, 2016, 893:1-19. doi:10.1007/978-3-319-24223-1_1.
[2]Dai C, Ren Y, Xie D, et al. Does Lymph Node Metastasis Have a Negative Prognostic Impact in Patients with NSCLC and M1a Disease?[J]. J ThoracOncol, 2016, 11(10):1745-1754. doi:10.1016/j. jtho.2016.06.030.
[3]Grun D, Adhikary G, Eckert RL. VEGF-A acts via neuropilin-1 to enhance epidermal cancer stem cell survival and formation of aggressive and highly vascularized tumors[J]. Oncogene, 2016, 35(33):4379-4387. doi:10.1038/onc.2015.507.
[4]Roth L, Prahst C, Ruckdeschel T, et al. Neuropilin-1 mediates vascular permeability independently of vascular endothelial growth factor receptor-2 activation[J]. Sci Signal,2016, 9(425):ra42. doi:10.1126/scisignal. aad3812.
[5]王金爽,黄建国,张建华,等.人非小细胞肺癌中神经纤毛蛋白1表达及其与临床病理特征和预后的关系[J].肿瘤, 2018, 38(5).
[6]Lu Y, Meng YG. Quantitation of Circulating Neuropilin-1 in Human, Monkey, Mouse, and Rat Sera by ELISA[J].Methods MolBiol, 2015, 1332:39-48. doi:10.1007/978-1-4939-2917-7_3.
[7]Torre LA, Siegel RL, Jemal A. Lung Cancer Statistics[J].Adv Exp Med Biol, 2016, 893:1-19. doi:10.1007/978-3-319-24223-1_1.
[8]Djordjevic S, Driscoll PC. Targeting VEGF signalling via the neuropilin co-receptor[J]. Drug Discov Today, 2013,18(9-10):447-455. doi:10.1016/j. drudis.2012.11.013.
[9]Lupo G, Caporarello N, Olivieri M, et al. Anti-angiogenic Therapy in Cancer:Downsides and New Pivots for Precision Medicine[J].Front Pharmacol, 2017, 7:519. doi:10.3389/fphar.2016.00519.
[10]Pichler R, Heidegger I. Novel concepts of antiangiogenic therapies in metastatic renal cell cancer[J]. Memo, 2017,10(4):206-212. doi:10.1007/s12254-017-0344-2.
[11]DjordjevicS, Driscoll PC. Targeting VEGF signalling via the neuropilin co-receptor[J]. Drug Discov Today, 2013,18(9-10):447-455. doi:10.1016/j. drudis.2012.11.013.
[12]Hong TM, Chen YL, Wu YY, et al. Targeting neuropilin 1 as an antitumor strategy in lung cancer[J]. Clin Cancer Res, 2007,13(16):4759-4768. doi:0.1158/1078-0432. CCR-07-0001.
[13]Jimenez-Hernandez LE, Vazquez-Santillan K, CastroOropeza R, et al. NRP1-positive lung cancer cells possess tumor-initiating properties[R]. Oncol Rep, 2018, 39(1):349-357. doi:10.3892/or.2017.6089.
[14]Ruffini F, Levati L, Graziani G, et al. Platelet-derived growth factor-C promotes human melanoma aggressiveness through activation of neuropilin-1[J]. Oncotarget, 2017,8(40):66833-66848. doi:10.18632/oncotarget.18706.
[15]Wu MH, Chen YL, Lee KH, et al. Glycosylation-dependent galectin-1/neuropilin-1 interactions promote liver fibrosis through activation of TGF-β-and PDGF-like signals in hepatic stellate cells[J]. Sci Rep, 2017, 7(1):11006. doi:10.1038/s41598-017-11212-1.
[16]Raimondi C, Fantin A, Lampropoulou A, et al. Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin1-dependent ABL1 activation in endothelial cells[J]. J Exp Med, 2014, 211(6):1167-1183. doi:10.1084/jem.20132330.
[17]Cimato T, Beers J, Ding S, et al. Neuropilin-1 identifies endothelial precursors in human and murine embryonic stem cells before CD34 expression[J]. Circulation, 2009, 119(16):2170-2178. doi:10.1161/CIRCULATIONAHA.109.849596.
[18]Lu Y, Meng YG. Quantitation of Circulating Neuropilin-1 in Human, Monkey, Mouse, and Rat Sera by ELISA[J]Methods MolBiol, 2015, 1332:39-48. doi:10.1007/978-1-4939-2917-7_3.
[19]Naik A, Al-Zeheimi N, Bakheit CS, et al. Neuropilin-1 Associated Molecules in the Blood Distinguish Poor Prognosis Breast Cancer:A Cross-Sectional Study[J]. Sci Rep, 2017,7(1):3301. doi:10.1038/s41598-017-03280-0.
[2]Dai C, Ren Y, Xie D, et al. Does Lymph Node Metastasis Have a Negative Prognostic Impact in Patients with NSCLC and M1a Disease?[J]. J ThoracOncol, 2016, 11(10):1745-1754. doi:10.1016/j. jtho.2016.06.030.
[3]Grun D, Adhikary G, Eckert RL. VEGF-A acts via neuropilin-1 to enhance epidermal cancer stem cell survival and formation of aggressive and highly vascularized tumors[J]. Oncogene, 2016, 35(33):4379-4387. doi:10.1038/onc.2015.507.
[4]Roth L, Prahst C, Ruckdeschel T, et al. Neuropilin-1 mediates vascular permeability independently of vascular endothelial growth factor receptor-2 activation[J]. Sci Signal,2016, 9(425):ra42. doi:10.1126/scisignal. aad3812.
[5]王金爽,黄建国,张建华,等.人非小细胞肺癌中神经纤毛蛋白1表达及其与临床病理特征和预后的关系[J].肿瘤, 2018, 38(5).
[6]Lu Y, Meng YG. Quantitation of Circulating Neuropilin-1 in Human, Monkey, Mouse, and Rat Sera by ELISA[J].Methods MolBiol, 2015, 1332:39-48. doi:10.1007/978-1-4939-2917-7_3.
[7]Torre LA, Siegel RL, Jemal A. Lung Cancer Statistics[J].Adv Exp Med Biol, 2016, 893:1-19. doi:10.1007/978-3-319-24223-1_1.
[8]Djordjevic S, Driscoll PC. Targeting VEGF signalling via the neuropilin co-receptor[J]. Drug Discov Today, 2013,18(9-10):447-455. doi:10.1016/j. drudis.2012.11.013.
[9]Lupo G, Caporarello N, Olivieri M, et al. Anti-angiogenic Therapy in Cancer:Downsides and New Pivots for Precision Medicine[J].Front Pharmacol, 2017, 7:519. doi:10.3389/fphar.2016.00519.
[10]Pichler R, Heidegger I. Novel concepts of antiangiogenic therapies in metastatic renal cell cancer[J]. Memo, 2017,10(4):206-212. doi:10.1007/s12254-017-0344-2.
[11]DjordjevicS, Driscoll PC. Targeting VEGF signalling via the neuropilin co-receptor[J]. Drug Discov Today, 2013,18(9-10):447-455. doi:10.1016/j. drudis.2012.11.013.
[12]Hong TM, Chen YL, Wu YY, et al. Targeting neuropilin 1 as an antitumor strategy in lung cancer[J]. Clin Cancer Res, 2007,13(16):4759-4768. doi:0.1158/1078-0432. CCR-07-0001.
[13]Jimenez-Hernandez LE, Vazquez-Santillan K, CastroOropeza R, et al. NRP1-positive lung cancer cells possess tumor-initiating properties[R]. Oncol Rep, 2018, 39(1):349-357. doi:10.3892/or.2017.6089.
[14]Ruffini F, Levati L, Graziani G, et al. Platelet-derived growth factor-C promotes human melanoma aggressiveness through activation of neuropilin-1[J]. Oncotarget, 2017,8(40):66833-66848. doi:10.18632/oncotarget.18706.
[15]Wu MH, Chen YL, Lee KH, et al. Glycosylation-dependent galectin-1/neuropilin-1 interactions promote liver fibrosis through activation of TGF-β-and PDGF-like signals in hepatic stellate cells[J]. Sci Rep, 2017, 7(1):11006. doi:10.1038/s41598-017-11212-1.
[16]Raimondi C, Fantin A, Lampropoulou A, et al. Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin1-dependent ABL1 activation in endothelial cells[J]. J Exp Med, 2014, 211(6):1167-1183. doi:10.1084/jem.20132330.
[17]Cimato T, Beers J, Ding S, et al. Neuropilin-1 identifies endothelial precursors in human and murine embryonic stem cells before CD34 expression[J]. Circulation, 2009, 119(16):2170-2178. doi:10.1161/CIRCULATIONAHA.109.849596.
[18]Lu Y, Meng YG. Quantitation of Circulating Neuropilin-1 in Human, Monkey, Mouse, and Rat Sera by ELISA[J]Methods MolBiol, 2015, 1332:39-48. doi:10.1007/978-1-4939-2917-7_3.
[19]Naik A, Al-Zeheimi N, Bakheit CS, et al. Neuropilin-1 Associated Molecules in the Blood Distinguish Poor Prognosis Breast Cancer:A Cross-Sectional Study[J]. Sci Rep, 2017,7(1):3301. doi:10.1038/s41598-017-03280-0.