MALAT-1和HIF-1α在三阴型乳腺癌中表达及临床意义
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摘要
目的探讨肺腺癌转移相关转录本-1(MALAT-1)、低氧诱导因子-1(HIF-1)αmRNA在三阴型乳腺癌(TNBC)中的表达及临床意义。方法采用免疫组织化学SP法检测HIF-1α的蛋白表达水平;实时荧光定量聚合酶链反应(RT-PCR)检测MALAT-1、HIF-1αmRNA的表达情况,分析其与TNBC临床特征的关系。结果 MALAT-1、HIF-1αmRNA在乳腺癌组织中的表达明显高于癌旁组织(2.62±0.23 vs.2.02±0.08;129.79±15.34 vs.43.46±5.14;P<0.05),HIF-1α蛋白在TNBC组织中的阳性表达率显著高于癌旁组织(69.7%vs.45.4%,P<0.05)。癌组织中的MALAT-1、HIF-1αmRNA的表达水平与TNBC组织的组织学分化程度、浸润深度、淋巴结转移、临床分期相关(P<0.01)。结论检测MALAT-1、HIF-1αmRNA的表达水平可能对TNBC浸润转移及增殖有一定的预测意义。
Objective To investigate the expression and clinical significance of metastasis-associated lung adenocarcinoma transcript 1(MALAT-1)and hypoxia inducible factor-1α(HIF-1α)in triple negative breast cancer(TNBC).Methods Immunohistochemical SP method was used to detect the expression of HIF-1αin 33 cases of TNBC tumor tissues and their corresponding paracancer tissues.HIF-α,MALAT-1 mRNA levels were measured by quantitative real-time PCR(RT-PCR).The correlation between HIF-1α,MALAT-1 levels and the clinical features of TNBC were analyzed.Results The expression of HIF-1α,MALAT-1 mRNA in breast tumor tissues was significantly higher than that in paracancer tissues in TNBC(2.62±0.23 vs.2.02±0.08;129.79±15.34 vs.43.46±5.14;P<0.05).The positive expression rate of HIF-1αin TNBC increased significantly compared with those in paracancer tissues(69.7%vs.45.4%,P<0.05).The positive expression rate of HIF-1α,MALAT-1 mRNA in TNBC patients correlated with histological grading,infiltration depth,lymph node metastasis,and clinical staging(P<0.01).Conclusion Detection of the expression level of MALAT-1 and HIF-1αmRNA may have some predictive significance for the invasion,metastasis and proliferation of TNBC.
Objective To investigate the expression and clinical significance of metastasis-associated lung adenocarcinoma transcript 1(MALAT-1)and hypoxia inducible factor-1α(HIF-1α)in triple negative breast cancer(TNBC).Methods Immunohistochemical SP method was used to detect the expression of HIF-1αin 33 cases of TNBC tumor tissues and their corresponding paracancer tissues.HIF-α,MALAT-1 mRNA levels were measured by quantitative real-time PCR(RT-PCR).The correlation between HIF-1α,MALAT-1 levels and the clinical features of TNBC were analyzed.Results The expression of HIF-1α,MALAT-1 mRNA in breast tumor tissues was significantly higher than that in paracancer tissues in TNBC(2.62±0.23 vs.2.02±0.08;129.79±15.34 vs.43.46±5.14;P<0.05).The positive expression rate of HIF-1αin TNBC increased significantly compared with those in paracancer tissues(69.7%vs.45.4%,P<0.05).The positive expression rate of HIF-1α,MALAT-1 mRNA in TNBC patients correlated with histological grading,infiltration depth,lymph node metastasis,and clinical staging(P<0.01).Conclusion Detection of the expression level of MALAT-1 and HIF-1αmRNA may have some predictive significance for the invasion,metastasis and proliferation of TNBC.
引文
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[19]赵文明,周炳娟,李金梅,等.HIF-1α、Glut-1表达与乳腺癌分化程度及分子亚型的关系[J].河北医学,2018,3(24):353-357.
[20]张峻,武月,赵岩,等.生物信息学分析沉默HIF-1α后胃癌细胞系基因表达变化同胃腺癌发生发展的相关性研究[J].现代肿瘤医学,2018,4(26):1155-1162.
[21]罗清,曾梓涵,赵玖,等.三阴性乳腺癌患者血清HO-TAIR、GAS5、MALAT-1表达变化及其意义[J].山东医药,2018,3(58):75-77.
[22]李子博,周江,周琳,等.乳腺癌组织中IncRNA、MAL-AT1的表达及临床意义[J].医学研究杂志,2018,3(47):79-81.
[23]徐益文,徐庆祥,丁义涛,缺氧诱导因子1与肿瘤的研究进展[J].医学综述,2012,6(18):1656-1660.
[2]CHEN S Y,SANG N L.Hypoxia-inducible factor-1:a critical player in the survival strategy of stressed cells[J].Cell Biochem,2016,117(2):267-278.
[3]ESPOSTI D D,HERNANDEZ-VARGAS H,VOEGELEC,et al.Identification of novel long non-coding RNAs deregulated inhepatocellular carcinoma using RNA-sequencing[J].Oncotarget,2016,7(22):31862-31877.
[4]FENG T,SHAO F,WU Q,et al.miR-124downregulation leads to breast cancer progression via LncRNA-MALAT1regulation and CDK4/E2F1signal activation[J].Oncotarget,2016,7(13):16205-16216.
[5]HUANG N S,CHI Y Y,XUE J Y,et al.Long non-coding RNA metas-tasis associated in lung adenocarcinoma transcript 1(MALAT1)interacts with estrogen receptor and predicted poor survival in breast cancer[J].Oncotarget,2016,7(25):37957-37965.
[6]徐益文,徐庆祥,丁义涛.缺氧诱导因子1与肿瘤的研究进展[J].医学综述,2012,6(18):1656-1660.
[7]SEMENZA G L.Defining the role of hypoxia-inducible factor 1in cancer biology and therapeutics[J].Oncogene,2010,29(5):625-634.
[8]JI P,DIEDERICHS S,WANG W,et al.MALAT-1,a novel noncoding RNA,and thymosin beta4predict metastasis and survival in early-stage non-small cell lung cancer[J].Oncogene,2003,22(39):8031-8041.
[9]CHOUDHRY H,SCHODEL J,OIKONOMOPOULOSS,et al.Exten-sive regulation of the non-coding transcriptome by hypox-ia:role of HIF in releasing paused RNApol2[J].EMBO Rep,2014,15(1):70-76.
[10]SHEN L,CHEN L,WANG Y,et al.Long noncoding RNA MALAT1promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer[J].Neurooncol,2015,121(1):101-108.
[11]KONISHI H,ICHIKAWA D,YAMAMOTO Y,et al.Plasma level of metastasis-associated lung adenocarcinoma transcript 1is associated with liver damage and predicts development of hepatocellular carcinoma[J].Cancer Sci,2016,107(2):149-154.
[12]LAI M C,YANG Z,ZHOU L,et al.Long non-coding RNA MALAT-1overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation[J].Med Oncol,2012,29(3):1810-1816.
[13]周俭珊,叶红.HIF-1α,VEGF及HIF-1α/VEGF轴在子宫内膜癌中的表达研究进展[J].海南医学,2015,26(16):2413-2416.
[14]刘彦琦,于红刚.缺氧诱导因子-1α和血管内皮生长因子在胃癌组织中的表达及其与肿瘤细胞增殖的关系[J].中华实验外科杂志,2015,32(9):2246-2248.
[15]孙慧霞,孙会,李国正.HIF-1α和Glut-1蛋白在中老年宫颈癌组织中的表达及其意义[J].中国妇产科临床杂志,2018,19(1):16-19.
[16]GUO F,GUO L,LI Y,et al.MALAT1is an oncogenic long non-coding RNA associated with tumor invasion in non-small cell lung cancer regulated by DNA methylation[J].Int J Clin Exp Pathol,2015,8(12):15903-15910.
[17]SHEN L,CHEN L,WANG Y,et al.Long noncoding RNAMAL-AT1promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer[J].J Neur Oncol,2015,1121(1):101-108.
[18]LI S,WANG Q,QIANG Q,et al.Sp1-mediated transcriptional regulation of MALAT1 plays a critical role in tumor[J].J Cancer Res Clin Oncol,2015,141(11):1909-1920.
[19]赵文明,周炳娟,李金梅,等.HIF-1α、Glut-1表达与乳腺癌分化程度及分子亚型的关系[J].河北医学,2018,3(24):353-357.
[20]张峻,武月,赵岩,等.生物信息学分析沉默HIF-1α后胃癌细胞系基因表达变化同胃腺癌发生发展的相关性研究[J].现代肿瘤医学,2018,4(26):1155-1162.
[21]罗清,曾梓涵,赵玖,等.三阴性乳腺癌患者血清HO-TAIR、GAS5、MALAT-1表达变化及其意义[J].山东医药,2018,3(58):75-77.
[22]李子博,周江,周琳,等.乳腺癌组织中IncRNA、MAL-AT1的表达及临床意义[J].医学研究杂志,2018,3(47):79-81.
[23]徐益文,徐庆祥,丁义涛,缺氧诱导因子1与肿瘤的研究进展[J].医学综述,2012,6(18):1656-1660.