神经纤毛蛋白-1在胃癌组织中的表达与临床病理特征及预后相关性的meta分析

doi:10.3760/cma.j.issn.1007-1245.2022.22.031

摘要/Abstract

摘要： 目的　通过meta分析评估神经纤毛蛋白（NRP）-1表达与胃癌临床病理特征及预后的相关性。方法　检索从建库至2022年4月在PubMed、Web of Science、Embase、The Cochrance Library、中国知网、万方、维普等数据库公开发表的关于胃癌中NRP-1表达的研究，根据纳入的文献，提取相关数据，使用软件RevMan 5.3和Stata 12进行统计分析。结果　共纳入13项研究包括1 635例胃癌患者。meta分析结果显示：NRP-1高表达与胃癌患者的不良预后有关（HR=1.66，95%CI 1.25～2.22，P=0.000 5），且与TNM分期（OR=0.37，95%CI 0.18～0.77，P=0.008）、分化程度（OR=0.43，95%CI 0.31～0.58，P<0.001）、淋巴结转移（OR=0.32，95%CI 0.16～0.63，P=0.000 9）、远处转移（OR=0.15，95%CI 0.06～0.39，P=0.000 1）有关，而与肿瘤长径（OR=0.40，95%CI 0.15～1.10，P=0.08）、肿瘤浸润程度（OR=0.44，95%CI 0.15～1.35，P=0.15）、Lauren分型（OR=0.73，95%CI 0.45～1.19，P=0.21）之间无明显关联。结论　NRP-1在胃癌中的表达与TNM分期、分化程度、淋巴结转移、远处转移有关。检测NRP-1的表达可能有助于判断胃癌患者的预后。

关键词: 胃癌, NRP-1, 临床病理特征, 预后, meta分析

Abstract: Objective　To evaluate the correlations between neuropilin (NRP)-1 expression and clinicopathological characteristics and prognosis of gastric cancer by meta-analysis. Methods　The researches on the expression of NRP-1 in gastric cancer published in PubMed, Web of Science, Embase, The Cochrance Library, CNKI, Wanfang, VIP, and other databases from the establishment of the database to April 2022 were retrieved. According to the included literatures, the relevant data were extracted. RevMan 5.3 and Stata12 software were used for the meta-analysis. Results　A total of 13 studies including 1 635 patients with gastric cancer were included. Meta-analysis showed that NRP-1 overexpression was associated with poor prognosis in patients with gastric cancer (HR=1.66, 95%CI 1.25-2.22, P=0.000 5), and was associated with TNM stage (OR=0.37, 95%CI 0.18-0.77, P=0.008), degree of differentiation (OR=0.43, 95%CI 0.31-0.58, P<0.001), lymph node metastasis (OR=0.32, 95%CI 0.16-0.63, P=0.000 9), and distant metastasis (OR=0.15, 95%CI 0.06-0.39, P=0.000 1), but there was no significant correlation with tumor size (OR=0.40, 95%CI 0.15-1.10, P=0.08), depth of invasion (OR=0.44, 95%CI 0.15-1.35, P=0.15), or Lauren's classification (OR=0.73, 95%CI 0.45-1.19, P=0.21). Conclusions　The expression of NRP-1 in gastric cancer is related to TNM stage, degree of differentiation, lymph node metastasis, and distant metastasis. Detecting the expression of NRP-1 may be helpful to judge the prognosis of patients with gastric cancer.

Key words: Gastric cancer, NRP-1, Clinicopathological characteristics, Prognosis, Meta-analysis

杨汉顾玉兰. 神经纤毛蛋白-1在胃癌组织中的表达与临床病理特征及预后相关性的meta分析[J]. 国际医药卫生导报, 2022, 28(22): 3246-3251.

Yang Han, Gu Yulan. Expression of NRP-1 in gastric cancer tissues and its correlations with clinicopathological characteristics and prognosis: a meta-analysis[J]. International Medicine and Health Guidance News, 2022, 28(22): 3246-3251.

参考文献

[1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. DOI: 10.3322/caac.21492.
[2] Hu C, Jiang X. Role of NRP-1 in VEGF-VEGFR2-independent tumorigenesis[J]. Target Oncol, 2016, 11(4): 501-505. DOI: 10.1007/s11523-016-0422-0.
[3] Plein A, Fantin A, Ruhrberg C. Neuropilin regulation of angiogenesis, arteriogenesis, and vascular permeability[J]. Microcirculation, 2014, 21(4): 315-323. DOI: 10.1111/micc.12124.
[4] Lin J, Zhang Y, Wu J, et al. Neuropilin 1 (NRP1) is a novel tumor marker in hepatocellular carcinoma[J]. Clin Chim Acta, 2018, 485: 158-165. DOI: 10.1016/j.cca.2018. 06.046.
[5] Morin E, Sjöberg E, Tjomsland V, et al. VEGF receptor-2/neuropilin 1 trans-complex formation between endothelial and tumor cells is an independent predictor of pancreatic cancer survival[J]. J Pathol, 2018, 246(3): 311-322. DOI: 10.1002/path.5141.
[6] Seifi-Alan M, Shams R, Bandehpour M, et al. Neuropilin-1 expression is associated with lymph node metastasis in breast cancer tissues[J]. Cancer Manag Res, 2018, 10: 1969-1974. DOI: 10.2147/CMAR.S169533.
[7] Staton CA, Koay I, Wu JM, et al. Neuropilin-1 and neuropilin-2 expression in the adenoma-carcinoma sequence of colorectal cancer[J]. Histopathology, 2013, 62(6): 908-915. DOI: 10.1111/his.12098.
[8] 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.
[9] Li L, Jiang X, Zhang Q, et al. Neuropilin-1 is associated with clinicopathology of gastric cancer and contributes to cell proliferation and migration as multifunctional co-receptors[J]. J Exp Clin Cancer Res, 2016, 35: 16. DOI: 10.1186/s13046-016-0291-5.
[10] 彭阳. NRP1在胃癌组织中的表达及抑制胃移植瘤生长的实验研究[D]. 重庆:重庆医科大学,2011. DOI:10.7666/d.Y2020041.
[11] Zhang L, Xing Y, Gao Q, et al. Combination of NRP1-mediated iRGD with 5-fluorouracil suppresses proliferation, migration and invasion of gastric cancer cells[J]. Biomed Pharmacother, 2017, 93: 1136-1143. DOI: 10.1016/j.biopha.2017.06.103.
[12] 杨少君. Neuropilins在胃癌组织中的表达及与临床病理特征和预后的关系[D]. 唐山: 河北联合大学, 2015.
[13] 史璇,张鑫,朱金朋,等. 胃腺癌组织中神经纤毛蛋白1、2的表达及意义[J]. 中国老年学杂志,2018,38(1):122-124. DOI:10.3969/j.issn.1005-9202.2018.01.049.
[14] 聂娜,吴小翎,俞慧宏,等. 胃癌组织中NRP1和NRP2表达情况及其与临床病理特征的相关性[J/CD]. 中国医学前沿杂志(电子版),2019,11(5):115-118. DOI:10.12037/YXQY.2019.05-27.
[15] 杨家佳,张琳,郑茂金,等. 胃癌中 VEGF、NRP1和干细胞标志物 CD44的表达及相关性[J]. 临床与实验病理学杂志, 2015, 31(2):124-127,131. DOI:10.13315/j.cnki.cjcep.2015.02.002.
[16] 张益明,赵茂森,朱仁武,等. Survivin、NRP1在胃癌中的表达及其对胃癌预后的影响[J]. 中国现代医生,2016,54(25):8-11,18,封3.
[17] Seo HS, Hyeon J, Song IH, et al. Relationship between neuropilin-1 expression and prognosis, according to gastric cancer histology[J]. J Mol Histol, 2020, 51(2): 199-208. DOI: 10.1007/s10735-020-09870-z.
[18] 范东伟,张晨嵩,姚昌洋,等. NRP-1在胃癌中的表达及临床意义[J]. 齐齐哈尔医学院学报,2018,39(6):625-628. DOI:10.3969/j.issn.1002-1256.2018.06.002.
[19] 韦世壮. Neuropilin-1在胃癌中的表达及在胃癌血管生成中的作用[D]. 南宁:广西医科大学,2006. DOI:10.7666/d.Y903324.
[20] 胡希宏, 王云忠, 金桂龙, 等. Neuropilin-1与胃癌发生、发展及血管生成的关系[J]. 浙江医学, 2013, 35(5): 347-350, 363.
[21] Jin Q, Ren Q, Chang X, et al. Neuropilin-1 predicts poor prognosis and promotes tumor metastasis through epithelial-mesenchymal transition in gastric cancer[J]. J Cancer, 2021, 12(12): 3648-3659. DOI: 10.7150/jca.52851.
[22] He Z, Tessier-Lavigne M. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III[J]. Cell, 1997, 90(4): 739-751. DOI: 10.1016/s0092-8674(00)80534-6.
[23] Kolodkin AL, Levengood DV, Rowe EG, et al. Neuropilin is a semaphorin III receptor[J]. Cell, 1997, 90(4): 753-762. DOI: 10.1016/s0092-8674(00)80535-8.
[24] Prud'homme GJ, Glinka Y. Neuropilins are multifunctional coreceptors involved in tumor initiation, growth, metastasis and immunity[J]. Oncotarget, 2012, 3(9): 921-939. DOI: 10.18632/oncotarget.626.
[25] Soker S, Takashima S, Miao HQ, et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor[J]. Cell, 1998, 92(6): 735-745. DOI: 10.1016/s0092-8674(00)81402-6.
[26] Peng Y, Liu YM, Li LC, et al. MicroRNA-338 inhibits growth, invasion and metastasis of gastric cancer by targeting NRP1 expression[J]. PLoS One, 2014, 9(4): e94422. DOI: 10.1371/journal.pone.0094422.
[27] Shi F, Shang L, Pan BQ, et al. Calreticulin promotes migration and invasion of esophageal cancer cells by upregulating neuropilin-1 expression via STAT5A[J]. Clin Cancer Res, 2014, 20(23): 6153-6162. DOI: 10.1158/1078-0432.CCR-14-0583.
[28] Tse BWC, Volpert M, Ratther E, et al. Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality[J]. Oncogene, 2017, 36(24): 3417-3427.
[29] Van Cutsem E, de Haas S, Kang YK, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial[J]. J Clin Oncol, 2012, 30(17): 2119-2127. DOI: 10.1200/JCO.2011.39.9824.
[30] Wang G, Shi B, Fu Y, et al. Hypomethylated gene NRP1 is co-expressed with PDGFRB and associated with poor overall survival in gastric cancer patients[J]. Biomed Pharmacother, 2019, 111: 1334-1341. DOI: 10.1016/j.biopha.2019.01.023.
[31] Zhang L, Xing Y, Gao Q, et al. Combination of NRP1-mediated iRGD with 5-fluorouracil suppresses proliferation, migration and invasion of gastric cancer cells[J]. Biomed Pharmacother, 2017, 93: 1136-1143. DOI: 10.1016/j.biopha.2017.06.103.
[32] Yang W, Lai Z, Li Y, et al. Immune signature profiling identified prognostic factors for gastric cancer[J]. Chin J Cancer Res, 2019, 31(3): 463-470. DOI: 10.21147/j.issn.1000-9604.2019.03.08.