乳腺癌组织中FGF-1、TIP30、TLR4、HIF-1α的表达及其与微血管密度的关系
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摘要
目的探讨乳腺癌组织中酸性成纤维细胞生长因子-1(FGF-1)、TIP30基因(TIP30)、Toll样受体4(TLR4)、缺氧诱导因子-1α(HIF-1α)的表达及其与微血管密度(MVD)的关系。方法选择2014年3月～2017年3月在曲靖市第一人民医院接诊的100例女性乳腺癌患者为研究对象。收集所有患者手术切除病理组织制作石蜡切片,使用SP免疫组织化学法观察乳腺癌组织中FGF-1、TIP30、TLR4、HIF-1α染色结果,并分析其与临床病理因素、MVD之间的关系。结果免疫组化结果显示,100例乳腺癌组织中,FGF-1阳性率为61.00%(61/100),TIP30阳性率为29.00%(29/100),TLR4阳性率为72.00%(72/100),HIF-1α阳性表达率为65.00%(65/100),且FGF-1、TIP30、TLR4、HIF-1α和肿瘤大小、临床分期、淋巴结转移之间均具有密切关系(P<0.05)。在FGF-1、TLR4及HIF-1α阳性组织中,MVD表达高于阴性组织;在TIP30阳性组织中MVD表达低于阴性组织(P<0.05)。相关性分析结果显示,FGF-1、TLR4及HIF-1α与MVD、肿瘤大小、临床分期、淋巴转移之间均呈正相关(P<0.05),而TIP30和MVD、肿瘤大小、临床分期、淋巴转移呈负相关(P<0.05)。结论在乳腺癌组织中,FGF-1、TLR4、HIF-1α的高表达和TIP30的低表达与MVD关系密切,可促使疾病进展,这为靶向药物治疗乳腺癌提供了新思路。
Objective To study expression of acidic fibroblast growth factor-1(FGF-1), TIP30 gene(TIP30), toll-like receptor 4(TLR4) and hypoxia inducible factor-1α(HIF-1α) in breast cancer tissues and its relationship with microvessel density(MVD). Methods 100 female breast cancer patients received therapy from March 2014 to March 2017 in our hospital were selected as research objects. They were collected and surgically removed, and paraffin sections were made. The dyeing result of FGF-1, TIP30, TLR4 and HIF-1α in breast cancer tissues were observed by SP immunohistochemistry. The relationship between MVD and clinical pathological factors was analyzed. Results In the immunohistochemcal in 100 cases of breast cancer tissue,the positive rate of FGF-1 was 61.00%(61/100), the positive rate of TIP30 was 29.00%(29/100),the positive rate of TLR4 was 72.00%(72/100),the positive rate of HIF-1α was 65.00%(65/100),and the FGF-1, TIP30, TLR4, HIF-1α and tumor size, clinical stage and lymh node metasis are closely ralated(P<0.05). The expression of MVD in FGF-1, TLR4 and HIF-1α positive tissues was significantly higher than that in negative tissues. The expression of MVD in TIP30 positive tissues was significantly lower than that in negative tissues(P<0.05). In the correlation analysis result, there was a positive correlation between FGF-1, TLR4 and HIF-1α with MVD, tumor size, clinical stage and lymph node metastasis(P<0.05), and there was a negative correlation between TIP30 with MVD, tumor size, clinical stage and lymph node metastasis(P<0.05). Conclusion In breast cancer, there is a close relationship between high expression of FGF-1, TLR4, HIF-1α and low expression of TIP30 with MVD, which can promote the progression of the disease.
Objective To study expression of acidic fibroblast growth factor-1(FGF-1), TIP30 gene(TIP30), toll-like receptor 4(TLR4) and hypoxia inducible factor-1α(HIF-1α) in breast cancer tissues and its relationship with microvessel density(MVD). Methods 100 female breast cancer patients received therapy from March 2014 to March 2017 in our hospital were selected as research objects. They were collected and surgically removed, and paraffin sections were made. The dyeing result of FGF-1, TIP30, TLR4 and HIF-1α in breast cancer tissues were observed by SP immunohistochemistry. The relationship between MVD and clinical pathological factors was analyzed. Results In the immunohistochemcal in 100 cases of breast cancer tissue,the positive rate of FGF-1 was 61.00%(61/100), the positive rate of TIP30 was 29.00%(29/100),the positive rate of TLR4 was 72.00%(72/100),the positive rate of HIF-1α was 65.00%(65/100),and the FGF-1, TIP30, TLR4, HIF-1α and tumor size, clinical stage and lymh node metasis are closely ralated(P<0.05). The expression of MVD in FGF-1, TLR4 and HIF-1α positive tissues was significantly higher than that in negative tissues. The expression of MVD in TIP30 positive tissues was significantly lower than that in negative tissues(P<0.05). In the correlation analysis result, there was a positive correlation between FGF-1, TLR4 and HIF-1α with MVD, tumor size, clinical stage and lymph node metastasis(P<0.05), and there was a negative correlation between TIP30 with MVD, tumor size, clinical stage and lymph node metastasis(P<0.05). Conclusion In breast cancer, there is a close relationship between high expression of FGF-1, TLR4, HIF-1α and low expression of TIP30 with MVD, which can promote the progression of the disease.
引文
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[6] 邱亚双,周慧芳.HIF-1α和VEGF在喉癌中的表达及其与血管生成的关系[J].临床耳鼻咽喉头颈外科杂志,2014,28(6):389-393.
[7] 中国抗癌协会乳腺癌专业委员会.中国抗癌协会乳腺癌诊治指南与规范(2015版)[J].中国癌症杂志,2015,25(9):692-754.
[8] 秦维香,张晓艳,马媛媛.免疫组化法用于肿瘤患者病理诊断的效果评价[J].中国实用医药,2016,11(11):31-32.
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[10] Mori N,Mugikura S,Takahashi S,et al.Quantitative Analysis of Contrast-Enhanced Ultrasound Imaging in Invasive Breast Cancer:A Novel Technique to Obtain Histopathologic Information of Microvessel Density[J].Ultrasound Med Biol,2017,43(3):607-614.
[11] 段羊羊,井明晰,徐君南,等.乳腺癌分子靶向治疗现状[J].中国肿瘤,2016,25(3):202-206.
[12] Shi H,Fu C,Wang W,et al.The FGF-1-specific single-chain antibody scFv1C9 effectively inhibits breast cancer tumour growth and metastasis[J].J Cell Mol Med,2014,18(10):2061-2070.
[13] 牟成金,汪静,张倩,等.FGF-1在乳腺癌中的表达与微血管生成的关系及临床意义[J].四川大学学报(医学版),2011,42(2):280-282
[14] 朱逸慜,谢忠.骨桥蛋白和TIP30与胃癌关系研究进展[J].中华实用诊断与治疗杂志,2013,27(5):423-425.
[15] 陈锦章,李祺,邓琼,等.Tip30调节EGFR核内化及其与核内EGFR靶分子或基因的关联性研究[J].中国临床研究,2015,28(1):7-10.
[16] Zhang C,Mori M,Gao S,et al.Tip30 deletion in MMTV-Neu mice leads to enhanced EGFR signaling and development of estrogen receptor-positive and progesterone receptor-negative mammary tumors[J].Cancer Res,2010,70(24):10224-10233.
[17] 黄水传,梁忠锃,张远起,等.TIP30在乳腺癌中的表达及其与血管生成的关系[J].广东医学,2013,34(9):1372-1375
[18] Chen X,Zhao F,Zhang H,et al.Significance of TLR4/MyD88 expression in breast cancer[J].Int J Clin Exp Pathol,2015,8(6):7034-7039.
[19] Volk-Draper L,Hall K,Griggs C,et al.Paclitaxel therapy promotes breast cancer metastasis in a TLR4-dependent manner[J].Cancer Res,2014,74(19):5421-5434.
[20] Li J,Yin J,Shen W,et al.TLR4 Promotes Breast Cancer Metastasis via Akt/GSK3β/β-Catenin Pathway upon LPS Stimulation[J].Anat Rec (Hoboken),2017,300(7):1219-1229.
[21] 卫文俊,张好云,王玉蓉,等.TLR4在乳腺癌组织中的表达与微血管密度的关系及临床意义[J].现代医学,2014,42(3):257-261.
[22] 安杰,刘伟,刘爽,等.HIF-1α及肿瘤相关巨噬细胞在乳腺癌组织中的表达及其意义[J].中国普通外科杂志,2014,23(11):1572-1575
[23] Qin J,Liu Y,Lu Y,et al.Hypoxia-inducible factor 1 alpha promotes cancer stem cells-like properties in human ovarian cancer cells by upregulating SIRT1 expression[J].Sci Rep,2017,7(1):10592
[24] 吴斯敏,刘志明,贺文兴,等.缺氧微环境下HIF-1α对乳腺癌上皮间质转化及侵袭迁移的影响[J].广西医科大学学报,2015,32(03):410-413.
[25] Wang L,Fan J,Yan CY,et al.Activation of hypoxia-inducible factor-1α by prolonged in vivo hyperinsulinemia treatment potentiates cancerous progression in estrogen receptor-positive breast cancer cells[J].Biochem Biophys Res Commun,2017,491(2):545-551.
[2] Nowak A,Grzegrzolka J,Paprocka M,et al.Nestin-positive microvessel density is an independent prognostic factor in breast cancer[J].Int J Oncol,2017,51(2):668-676.
[3] Lobocki M,Zakrzewska M,Szlachcic A,et al.High-Yield Site-Specific Conjugation of Fibroblast Growth Factor 1 with Monomethylauristatin E via Cysteine Flanked by Basic Residues[J].Bioconjug Chem,2017,28(7):1850-1858
[4] 李浩,吴金术,蒋波,等.Tip30基因表达对肝癌细胞侵袭转移能力的影响[J].中南大学学报(医学版),2014,39(8):775-783Li H,Wu JS,Jiang B,et al.Effect of Tip30 expression on the invasion and metastasis of hepatoma cells[J].Journal of Central South University(Medical Science),2014,39(8):775-783
[5] Wang X,Yu X,Wang Q,et al.Expression and clinical significance of SATB1 and TLR4 in breast cancer[J].Oncol Lett,2017,14(3):3611-3615.
[6] 邱亚双,周慧芳.HIF-1α和VEGF在喉癌中的表达及其与血管生成的关系[J].临床耳鼻咽喉头颈外科杂志,2014,28(6):389-393.
[7] 中国抗癌协会乳腺癌专业委员会.中国抗癌协会乳腺癌诊治指南与规范(2015版)[J].中国癌症杂志,2015,25(9):692-754.
[8] 秦维香,张晓艳,马媛媛.免疫组化法用于肿瘤患者病理诊断的效果评价[J].中国实用医药,2016,11(11):31-32.
[9] Nematolahi S,Rezaianzadeh A,Zare N,et al.Prognostic Factors of Breast Cancer Survival in the Islamic Republic of Iran:an Additive Empirical Bayesian Approach[J].East Mediterr Health J,2018,23(11):721-728.
[10] Mori N,Mugikura S,Takahashi S,et al.Quantitative Analysis of Contrast-Enhanced Ultrasound Imaging in Invasive Breast Cancer:A Novel Technique to Obtain Histopathologic Information of Microvessel Density[J].Ultrasound Med Biol,2017,43(3):607-614.
[11] 段羊羊,井明晰,徐君南,等.乳腺癌分子靶向治疗现状[J].中国肿瘤,2016,25(3):202-206.
[12] Shi H,Fu C,Wang W,et al.The FGF-1-specific single-chain antibody scFv1C9 effectively inhibits breast cancer tumour growth and metastasis[J].J Cell Mol Med,2014,18(10):2061-2070.
[13] 牟成金,汪静,张倩,等.FGF-1在乳腺癌中的表达与微血管生成的关系及临床意义[J].四川大学学报(医学版),2011,42(2):280-282
[14] 朱逸慜,谢忠.骨桥蛋白和TIP30与胃癌关系研究进展[J].中华实用诊断与治疗杂志,2013,27(5):423-425.
[15] 陈锦章,李祺,邓琼,等.Tip30调节EGFR核内化及其与核内EGFR靶分子或基因的关联性研究[J].中国临床研究,2015,28(1):7-10.
[16] Zhang C,Mori M,Gao S,et al.Tip30 deletion in MMTV-Neu mice leads to enhanced EGFR signaling and development of estrogen receptor-positive and progesterone receptor-negative mammary tumors[J].Cancer Res,2010,70(24):10224-10233.
[17] 黄水传,梁忠锃,张远起,等.TIP30在乳腺癌中的表达及其与血管生成的关系[J].广东医学,2013,34(9):1372-1375
[18] Chen X,Zhao F,Zhang H,et al.Significance of TLR4/MyD88 expression in breast cancer[J].Int J Clin Exp Pathol,2015,8(6):7034-7039.
[19] Volk-Draper L,Hall K,Griggs C,et al.Paclitaxel therapy promotes breast cancer metastasis in a TLR4-dependent manner[J].Cancer Res,2014,74(19):5421-5434.
[20] Li J,Yin J,Shen W,et al.TLR4 Promotes Breast Cancer Metastasis via Akt/GSK3β/β-Catenin Pathway upon LPS Stimulation[J].Anat Rec (Hoboken),2017,300(7):1219-1229.
[21] 卫文俊,张好云,王玉蓉,等.TLR4在乳腺癌组织中的表达与微血管密度的关系及临床意义[J].现代医学,2014,42(3):257-261.
[22] 安杰,刘伟,刘爽,等.HIF-1α及肿瘤相关巨噬细胞在乳腺癌组织中的表达及其意义[J].中国普通外科杂志,2014,23(11):1572-1575
[23] Qin J,Liu Y,Lu Y,et al.Hypoxia-inducible factor 1 alpha promotes cancer stem cells-like properties in human ovarian cancer cells by upregulating SIRT1 expression[J].Sci Rep,2017,7(1):10592
[24] 吴斯敏,刘志明,贺文兴,等.缺氧微环境下HIF-1α对乳腺癌上皮间质转化及侵袭迁移的影响[J].广西医科大学学报,2015,32(03):410-413.
[25] Wang L,Fan J,Yan CY,et al.Activation of hypoxia-inducible factor-1α by prolonged in vivo hyperinsulinemia treatment potentiates cancerous progression in estrogen receptor-positive breast cancer cells[J].Biochem Biophys Res Commun,2017,491(2):545-551.