缺氧诱导因子1α在非小细胞肺癌组织中的表达及其与患者临床预后的关系
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摘要
目的观察缺氧诱导因子1α(HIF-1α)在非小细胞肺癌组织中的表达及其与患者临床预后的关系。方法选取2015年1月至2017年1月于武装警察部队后勤学院附属医院首诊新发非小细胞肺癌患者120例。使用免疫组织化学法测定患者初诊肺活检组织中HIF-1α蛋白表达水平,并收集患者1年随访的短期预后情况,分析HIF-1α表达对转移/复发以及死亡的影响。结果 HIF-1α阳性患者中血管内皮生长因子(VEGF)和VEGF受体2 (VEGFR2)阳性者比例均高于HIF-1α阴性患者[77.3%(68/88)比65. 6%(21/32)、75. 0%(66/88)比62. 5%(20/32)],差异均有统计学意义(均P<0.05)。随访1年间共有17例患者转移/复发,HIF-1α阳性患者的转移/复发率高于HIF-1α阴性患者[17. 0%(15/88)比6. 2%(2/32)],差异有统计学意义(P<0. 05);有6例患者死亡,其中4例HIF-1α阳性,2例HIF-1α阴性。Logistic回归分析结果显示,HIF-1α阳性以及VEGF和VEGFR2阳性均为首诊新发非小细胞肺癌患者转移/复发、死亡以及合计不良预后的危险因素,比值比均大于1,均P<0.05。结论 HIF-1α阳性以及VEGF和VEGFR2阳性均为非小细胞癌转移/复发、死亡以及合计不良预后的危险因素。
Objective To investigate the expression of hypoxia inducible factor-la(HIF-1α) in non-small cell lung cancer and the impact on prognosis. Methods From January 2015 to January 2017, 120 patients with newly diagnosed non-small cell lung cancer in the Affiliated Hospital of Logistics College of Chinese People's Armed Police Forces were enrolled. Expression of HIF-lα in lung biopsy tissue was tested by immunohistochemistry.Prognosis of patients was observed in 1 year after discharge. The relation between HIF-1α expression and metastasis/recurrence or death was analyzed. Results Positive rates of vascular endothelial growth factor( VEGF) and VEGF receptor 2(VEGFR2) in HIF-la positive patients were significantly higher than those in HIF-la negative patients[77. 3%(68/88) vs 65. 6%( 21/32)) 75. 0%(66/88) vs 62. 5%(20/32) ]( P < 0. 05). During 1-year follow-up, 17 patients had metastasis or recurrence; the rate of metastasis/recurrence in HIF-1α positive patients was significantly higher than that in HIF-1α negative patients[ 17.0%(15/88) vs 6. 2%(2/32) ](P < 0. 05).There were 6 deaths., including 4 cases of HIF-1α positive and 2 cases of HIF-1α negative. Logistic regression analysis suggested that HIF-1 a, VEGF and VEGFR2 positive expression were risk factors of metastasis/recurrence and death in non-small cell lung cancer patients(odds ratio > 1, P < 0. 05). Conclusion HIF-1α, VEGF and VEGFR2 positive expression are risk factors of metastasis, recurrence and death in non-small cell lung cancer atients.
Objective To investigate the expression of hypoxia inducible factor-la(HIF-1α) in non-small cell lung cancer and the impact on prognosis. Methods From January 2015 to January 2017, 120 patients with newly diagnosed non-small cell lung cancer in the Affiliated Hospital of Logistics College of Chinese People's Armed Police Forces were enrolled. Expression of HIF-lα in lung biopsy tissue was tested by immunohistochemistry.Prognosis of patients was observed in 1 year after discharge. The relation between HIF-1α expression and metastasis/recurrence or death was analyzed. Results Positive rates of vascular endothelial growth factor( VEGF) and VEGF receptor 2(VEGFR2) in HIF-la positive patients were significantly higher than those in HIF-la negative patients[77. 3%(68/88) vs 65. 6%( 21/32)) 75. 0%(66/88) vs 62. 5%(20/32) ]( P < 0. 05). During 1-year follow-up, 17 patients had metastasis or recurrence; the rate of metastasis/recurrence in HIF-1α positive patients was significantly higher than that in HIF-1α negative patients[ 17.0%(15/88) vs 6. 2%(2/32) ](P < 0. 05).There were 6 deaths., including 4 cases of HIF-1α positive and 2 cases of HIF-1α negative. Logistic regression analysis suggested that HIF-1 a, VEGF and VEGFR2 positive expression were risk factors of metastasis/recurrence and death in non-small cell lung cancer patients(odds ratio > 1, P < 0. 05). Conclusion HIF-1α, VEGF and VEGFR2 positive expression are risk factors of metastasis, recurrence and death in non-small cell lung cancer atients.
引文
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[11]高世乐,胡宗涛.血管内皮生长因子和黏附分子蛋白CD44变异体6与非小细胞肺癌同步放化疗近期疗效的相关性[J].中国医药,2017,12(10):1507-1510.DOI:10.3760/cma.j.issn. 16734777.2017. 10.017.Gao SL, Hu ZT. Relation among vascular endothelial growth factor, adhesion molecule protein CD44 v6 and short-term outcome of chemoradiotherapy in patients with non-small-cell lung cancer[J].China Medicine, 2017,12(10):1507-1510. DOI:10. 3760/cma. j.issn. 1673-4777.2017.10.017.
[12]李传贵.HIF-1α和VEGF在非小细胞肺癌中表达及临床意义[D].石家庄:河北医科大学,2015.Li CG. Expression and clinical significance of HIF-la and VEGF in non-small cell lung cancer[D]. Shijiazhuang:Hebei Medical University, 2015.
[13]方志红,李天苗,许荣忠,等.246例非小细胞肺癌的预后影响因素分析[J].现代肿瘤医学,2017,25(8):1234-1236.DOI:10.3969/j. issn. 1672-4992.2017.08.015.Fang ZH,Li TM, Xu RZ,et al. Analysis of prognostic factors in246 patients with non-small cell lung cancer[J]. Journal of Modern Oncology, 2017,25(8):1234-1236. DOI:10. 3969/j. issn. 1672-4992.2017.08.015.
[2]杜美琳,张毅,白雪,等.mTOR抑制剂雷帕霉素对肺癌LK2细胞的抑制作用[J].实用药物与临床,2017,20(7):741-743.DOI:10.14053/j. cnki. ppcr. 201707003.Du ML, Zhang Y, Bai X, et al. Inhibitory effects of rapamycin on lung cancer LK2 cells[J]. Practical Pharmacy and Clinical Remedies,2017,20(7):741-743. DOI:10.14053/j. cnki. ppcr. 201707003.
[3]邢国凤.周围型肺癌的CT成像及病理特征与血管内皮生长因子表达的相关性研究[J].中国临床医生杂志,2016,44(4):58-61. DOI:10.3969/j. issn.2095-8552.2016.04.019.Xing GF. Correlation between CT imaging and pathological features and expression of vascular endothelial growth factor in peripheral lung cancer[J]. Chinese Journal for Clinicians, 2016,44(4):58-61. DOI:10.3969/j. issn. 2095-8552.2016.04.019.
[4]宋雅妹,王晶.炎症与肺癌的相关性研究[J].中国临床医生杂志,2017,45(4):16-18. DOI:10. 3969/j. issn. 2095-8552.2017.04.007.Song YM, Wang J. Correlation between inflammation and lung cancer[J]. Chinese Journal for Clinicians, 2017,45(4):16-18.DOI:10.3969/j. issn.2095-8552.2017.04.007.
[5]徐怀阳,钟竑,陆善伟,等.HIF-1a与非小细胞肺癌增殖、血管生成及预后的关系[J].临床肺科杂志,2014,19(1):73-76.DOI:10.3969/j. issn. 1009-6663.2014.01.025.Xu HY, Zhong H, Lu SW, et al. Correlation of expression of HIF-1a to proliferation and neovascularization of tumor and prognosis of patients with non-small cell lung cancer[J]. Journal of Clinical Pulmonary Medicine, 2014, 19(1):73-76. DOI:10.3969/j. issn. 1009-6663.2014.01.025.
[6]徐秋萍,何斐,刘志强,等.性别对非小细胞肺癌预后的影响分析[J].中华流行病学杂志,2017,38(2):244-247.DOI:10.3760/cma. j. issn. 0254-6450.2017.02. 022.Xu QP, He F, Liu ZQ, et al. Effect of gender on the prognosis of patients with non-small cell lung cancer[J]. Chinese Journal of Epidemiology, 2017,38(2):244-247. DOI:10. 3760/cma. j.issn. 0254-6450.2017.02.022.
[7]王辉,侯炜,孙桂芝,等.晚期恶性肿瘤营养不良患者中医虚证证候特征的调查研究[J].世界中医药,2016,11(12):2793-2796. DOI:10.3969/j. issn. 1673-7202.2016.12.070.Wang H, Hou W, Sun GZ, et al. Distribution Characteristics of Deficiency Syndromes of Chinese Medicine in Patients have Advanced Malignant Tumor with Malnutrition[J]. World Chinese Medicine, 2016,11(12):2793-2796. DOI:10. 3969/j. issn.1673-7202.2016.12.070.
[8]赵涵,黄伟,解玉卓,等.MDMX对非小细胞肺癌放疗抵抗性的研究进展[J].实用药物与临床,2018,21(3):330-332. DOI:10.14053/j. cnki. ppcr. 201803024.Zhao H, Huang W, Xie YZ, et al. Progress of MDMX in the treat-ment of non-small cell lung cancer with radiotherapy resistance[J].Practical Pharmacy and Clinical Remedies, 2018,21(3):330-332. DOI:10.14053/j.cnki.ppcr. 201803024.
[9]黄磊.肺癌病证与现代检测指标的相关性研究[D].南京:南京中医药大学,2014.Huang L. Correlation between lung cancer syndromes and modern detection indexes[D]. Nanjing:Nanjing University of Chinese Medicine, 2014.
[10]王维,李强,韩青松,等.HIF-α、VEGF和DLL4在非小细胞肺癌中的表达及临床意义[J].解放军医药杂志,2016,28(5):44-47,53. DOI:10.3969/j. issn.2095-140X.2016.05.011.Wang W, Li Q, Han QS, et al. Expressions and clinical significance of HIF-a,VEGF and DLL4 in non-small cell lung cancer[J].Medical&Pharmaceutical Journal of Chinese People's Liberation Army, 2016,28(5):4447,53. DOI:10. 3969/j. issn. 2095-140X.2016.05.011.
[11]高世乐,胡宗涛.血管内皮生长因子和黏附分子蛋白CD44变异体6与非小细胞肺癌同步放化疗近期疗效的相关性[J].中国医药,2017,12(10):1507-1510.DOI:10.3760/cma.j.issn. 16734777.2017. 10.017.Gao SL, Hu ZT. Relation among vascular endothelial growth factor, adhesion molecule protein CD44 v6 and short-term outcome of chemoradiotherapy in patients with non-small-cell lung cancer[J].China Medicine, 2017,12(10):1507-1510. DOI:10. 3760/cma. j.issn. 1673-4777.2017.10.017.
[12]李传贵.HIF-1α和VEGF在非小细胞肺癌中表达及临床意义[D].石家庄:河北医科大学,2015.Li CG. Expression and clinical significance of HIF-la and VEGF in non-small cell lung cancer[D]. Shijiazhuang:Hebei Medical University, 2015.
[13]方志红,李天苗,许荣忠,等.246例非小细胞肺癌的预后影响因素分析[J].现代肿瘤医学,2017,25(8):1234-1236.DOI:10.3969/j. issn. 1672-4992.2017.08.015.Fang ZH,Li TM, Xu RZ,et al. Analysis of prognostic factors in246 patients with non-small cell lung cancer[J]. Journal of Modern Oncology, 2017,25(8):1234-1236. DOI:10. 3969/j. issn. 1672-4992.2017.08.015.