Expression and clinical significance of neuropilin-1 in EGFR positive lung adenocarcinoma
-
摘要: 目的 初步探索神经纤毛蛋白-1(NRP-1)在表皮生长因子受体(EGFR)阳性肺腺癌中的表达及临床意义。方法 筛选我院经手术切除并行病理学及基因检测确诊为肺腺癌EGFR阳性的54例及阴性的28例石蜡包埋标本,应用免疫组织化学法检测NRP-1、血管内皮生长因子受体2(VEGFR2)的表达,比较分析各临床指标与NRP-1、VEGFR2的相关性。结果 NRP-1、VEGFR2在EGFR阳性肺腺癌组织的阳性表达率均明显高于EGFR阴性肺腺癌组织(P<0.05)。NRP-1、VEGFR2在EGFR阳性肺腺癌组织中的表达与肿瘤直径、TNM分期、肿瘤组织分化程度和淋巴结转移有关(P<0.05),与患者年龄和性别无关(P>0.05)。Kaplan-Meier生存曲线显示EGFR阳性肺腺癌患者中NRP-1和VEGFR2低表达组的无进展生存时间(PFS)明显长于高表达组(P<0.05)。NRP-1和VEGFR2的表达呈正相关。COX多因素分析显示NRP-1与VEGFR2均是EGFR阳性肺腺癌患者不良预后的独立危险因素(P<0.05)。结论 NRP-1在EGFR阳性肺腺癌组织中高表达,NRP-1有可能成为EGFR阳性肺腺癌靶向治疗的新靶点。
-
关键词:
- 表皮生长因子受体突变 /
- 肺腺癌 /
- 神经纤毛蛋白 /
- 血管内皮生长因子 /
- 免疫组织化学
Abstract: Objective To explore the expression and clinical significance of neuropilin-1 (NRP-1) in epidermal growth factor receptor (EGFR)-positive lung adenocarcinoma. Methods Fifty cases with positive EGFR mutation and 28 cases with negative EGFR mutation were screened. The expression of NRP-1 and VEGFR2 was detected by immunohistochemistry. The correlation between clinical parameters and NRP-1 and VEGFR2 was analyzed. Results The positive expression rates of NRP-1 and VEGFR2 in EGFR mutant positive lung adenocarcinoma were significantly higher than those in EGFR mutant negative lung adenocarcinoma (P<0.05). The expression of NRP-1 and VEGFR2 in EGFR-positive lung adenocarcinoma was correlated with the size of tumors, TNM stage, differentiation degree of tumors and lymph node metastasis (P<0.05), but not with age and sex (P>0.05). Kaplan-Meier survival curve showed that progression-free survival (PFS) in low-expression group of NRP-1 and VEGFR2 was significantly longer than that in high-expression group (P < 0.05). The expression of NRP-1 and VEGFR2 was positively correlated. COX multivariate analysis showed that both NRP-1 and VEGFR2 were independent risk factors for poor prognosis of EGFR-positive lung adenocarcinoma patients (P<0.05). Conclusions NRP-1 is highly expressed in EGFR-positive lung adenocarcinoma tissues. NRP-1 plays an important role in the occurrence, development and metastasis of lung adenocarcinoma. NRP-1 may be a new target for targeted therapy of EGFR-positive lung adenocarcinoma. -
-
[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] 张萍, 武晓楠, 聂鑫,等. 晚期肺腺癌EGFR基因突变及临床特征分析[J]. 实用肿瘤杂志, 2018, 33(2): 150-153. [3] Soker S, Miao HQ, Nomi M, et al. VEGF165 mediates formation of complexes containing VEGFR-2 and neuropilin-1 that enhance VEGF165-receptor binding[J]. J Cell Biochem, 2002, 85(2): 357-368. DOI: 10.1002/jcb.10140.
[4] Pilkington G, Boland A, Brown T, et al. A systematic review of the clinical effectiveness of first-line chemotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer[J]. Thorax, 2015, 70(4): 359-367. DOI: 10.1136/thoraxjnl-2014-205914.
[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): 452-459. DOI: 10.3781/j.issn.1000-7431.2018.33.048. [6] Kawakami T, Tokunaga T, Hatanaka H, et al. Neuropilin 1 and neuropilin 2 co-expression is significantly correlated with increased vascularity and poor prognosis innonsmall cell lung carcinoma[J]. Cancer, 2002, 95(10): 2196-2201. DOI: 10.1002/cncr.10936.
[7] 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: 10.1158/1078-0432.CCR-07-0001.
[8] Wu YL, Lee JS, Thongprasert S, et al. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2):a randomised, double-blind trial[J]. Lancet Oncol, 2013, 14(8): 777-786. DOI: 10.1016/S1470-2045(13)70254-7.
[9] 刘洋, 熊志成, 孙鑫, 等. 奥希替尼联合抗血管生成靶向药对人肺腺癌细胞抑制作用的实验研究[J]. 现代肿瘤医学, 2018, 26(19): 3003-3008. DOI: 10.3969/j.issn.1672-4992.2018.19.002. [10] Yoshida K, Yamada Y. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harboring EGFR mutations (JO25567): an open-label, randomized, multicenter, phase Ⅱ study[J]. Transl Lung Cancer Res, 2015, 4(3): 217-219. DOI: 10.3978/j.issn.2218-6751.2015.03.04.
[11] Guttmann-Raviv N, Kessler O, Shraga-Heled N, et al. The neuropilins and their role in tumorigenesis and tumor progression[J]. Cancer Lett, 2006, 231(1): 1-11. DOI: 10.1016/j.canlet.2004.12.047.
[12] Xu L,Duda DG, di Tomaso E, et al. Direct evidence that bevacizumab, an anti-VEGF antibody, up-regulates SDF1α, CXCR4, CXCL6, and neuropilin 1 in tumors from patients with rectal cancer[J]. Cancer Res, 2009, 69(20): 7905-7910. DOI: 10.1158/0008-5472.CAN-09-2099.
[13] Raimondi C, Fantin A, Lampropoulou A, et al. Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells[J]. J Exp Med, 2014, 211(6): 1167-1183. DOI: 10.1084/jem.20132330.
[14] Cao S, Yaqoob U, Das A, et al. Neuropilin-1 promotes cirrhosis of the rodent and human liver by enhancing PDGF/TGF-β signaling in hepatic stellate cells[J]. J Clin Invest, 2010, 120(7): 2379-2394. DOI: 10.1172/JCI41203.
[15] Mo N,Lu YK, Xie WM, et al. Inhibition of autophagy enhances the radiosensitivity of nasopharyngeal carcinoma by reducing Rad51 expression[J]. Oncol Rep, 2014, 32(5): 1905-1912. DOI: 10.3892/or.2014.3427.
[16] 陈晖, 蒋晓东. NRP-1介导的非依赖VEGF-VEGFR2通路在肿瘤发生发展中的作用[J]. 临床肿瘤学杂志, 2015, 20(10): 948-952. [17] Jin Y, Li JP, TangLY, et al. Protein expression and significance of VEGF, EGFR and MMP-9 in non-small cell lung carcinomas[J]. Asian Pac J Cancer Prev, 2011, 12(6): 1473-1476.
[18] 孟谊, 杨杨, 樊祥山, 等. VEGF、EGFR的表达与非小细胞肺癌生物学行为的相关性[J]. 现代肿瘤医学, 2015, 23(5): 633-636. DOI: 10.3969/j.issn.1672-4992.2015.05.16. [19] Akagi M, Kawaguchi M, Liu W, et al. Induction of neuropilin-1 and vascular endothelial growth factor by epidermal growth factor in human gastric cancer cells[J].Br J Cancer, 2003, 88(5): 796-802. DOI: 10.1038/sj.bjc.6600811.
计量
- 文章访问数: 1700
- HTML全文浏览量: 1
- PDF下载量: 97
下载:
.png)
