转录因子Hey1在非小细胞肺癌中的表达及临床意义
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摘要
目的检测Hey1与Notch1在非小细胞肺癌组织中的表达,探讨Hey1在非小细胞肺癌中的表达与Notch1的表达、各临床病理特征之间的关系。方法制作组织芯片,采用免疫组织化学染色检测Notch1和Hey1在246例非小细胞肺癌组织及相应117例癌旁正常肺组织中的表达,应用SPSS 21.0进行统计分析。结果 Notch1在肺鳞癌、肺腺癌和癌旁正常肺组织的阳性率分别为78.8%,28.9%和30.8%,Hey1在肺鳞癌、肺腺癌和癌旁正常肺组织中的阳性率分别为79.7%,23.4%和33.3%;肺鳞癌患者Notch1阳性表达与TNM分期和淋巴结转移情况呈正相关;肺鳞癌患者Hey1阳性表达与TNM分期呈正相关,与肿瘤分化程度呈负相关;Spearman相关分析显示,肺鳞癌和肺腺癌组织中Notch1表达与Hey1表达具有显著的正相关关系。结论 Hey1和Notch1与肺鳞癌的恶性程度密切相关,可能是肺鳞癌发生、发展的重要参与因子。
Objective To examine the expression of Hey1 and Notch1 in non-small cell lung cancer tissues(NSCLC) and investigate its relationship with the expression of Notch1 and clinical pathological features. Methods Tissue microarray was prepared and immunohistochemical staining was used to detect the expression of Notch1 and Hey1 in 246 cases of NSCLC tissues and 117 adjacent normal lung tissues. SPSS 21.0 was used for statistical analysis. Results The positive rates of Notch1 in lung squamous cell carcinoma,lung adenocarcinoma and adjacent normal lung tissues were 78.8%, 28.9% and 30.8%, respectively, and the positive rates of Hey1 in lung squamous cell carcinoma, lung adenocarcinoma and adjacent normal lung tissues were 79.7%, 23.4% and 33.3%, respectively.The positive expression of Notch1 in lung squamous cell carcinoma was positively correlated with TNM staging and lymph node metastasis. The positive expression of Hey1 in lung squamous cell carcinoma was positively correlated with TNM staging and negatively correlated with tumor differentiation. Spearman correlation analysis showed that there was a significant positive correlation between Notch1 expression and Hey1 expression in lung squamous cell carcinoma and lung adenocarcinoma tissues. Conclusion Hey1 and Notch1 are closely related to the malignant degree of lung squamous cell carcinoma, which may be an important factor in the tumorigenesis and development of lung squamous cell carcinoma.
Objective To examine the expression of Hey1 and Notch1 in non-small cell lung cancer tissues(NSCLC) and investigate its relationship with the expression of Notch1 and clinical pathological features. Methods Tissue microarray was prepared and immunohistochemical staining was used to detect the expression of Notch1 and Hey1 in 246 cases of NSCLC tissues and 117 adjacent normal lung tissues. SPSS 21.0 was used for statistical analysis. Results The positive rates of Notch1 in lung squamous cell carcinoma,lung adenocarcinoma and adjacent normal lung tissues were 78.8%, 28.9% and 30.8%, respectively, and the positive rates of Hey1 in lung squamous cell carcinoma, lung adenocarcinoma and adjacent normal lung tissues were 79.7%, 23.4% and 33.3%, respectively.The positive expression of Notch1 in lung squamous cell carcinoma was positively correlated with TNM staging and lymph node metastasis. The positive expression of Hey1 in lung squamous cell carcinoma was positively correlated with TNM staging and negatively correlated with tumor differentiation. Spearman correlation analysis showed that there was a significant positive correlation between Notch1 expression and Hey1 expression in lung squamous cell carcinoma and lung adenocarcinoma tissues. Conclusion Hey1 and Notch1 are closely related to the malignant degree of lung squamous cell carcinoma, which may be an important factor in the tumorigenesis and development of lung squamous cell carcinoma.
引文
[1]Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin, 2017, 67(1):7-30.
[2]Bernhardt M, Galach M, Novak D, et al. Mediators of induced pluripotency and their role in cancer cells-current scientific knowledge and future perspectives. Biotechnol J,2012, 7(6):810-821.
[3]Zanotti S, Canalis E. Notch and the skeleton. Mol Cell Biol,2010, 30(4):886-896.
[4]Leong KG, Karsan A. Recent insights into the role of Notch signaling in tumorigenesis. Blood, 2006, 107(6):2223-2233.
[5]Liu TJ, Gao YH, Sakamoto K. BMP-2 Promotes Differentiation of Osteoblasts and Chondroblasts in Runx2-Deficient Cell Lines. J Cell Physiol, 2007, 211(3):728-735.
[6]Camilla D, Andries B, Gavin C. Functional Notch signaling is required for BMP4-induced inhibition of myogenic differentiation. Development, 2003, 130(24):6089-6099.
[7]Tsuru A, Setoguchi T, Matsunoshita Y, et al. Hairy/enhancerof-split related with YRPW motif protein 1 promotes osteosarcoma metastasis via matrix metallopeptidase 9 expression. Br J Cancer, 2015, 112(7):1232-1240.
[8]Candy PA, Phillips MR, Redfern AD, et al. Notch-induced transcription factors are predictive of survival and 5-fluorouracil response in colorectal cancer patients. Br J Cancer,2013, 109(4):1023-1030.
[9]Mann CD, Bastianpillai C, Neal CP, et al. Notch3 and HEY-1 as prognostic biomarkers in pancreatic adenocarcinoma.PLoS One, 2012, 7(12):e51119.
[10] Jung CW, Kong JS, Seol H, et al. Expression of activated Notch1 and Hey1 in papillary thyroid carcinoma. Histopathology, 2017, 70(2):301-308.
[11] Hulleman E, Quarto M, Vernell R, et al. A role for the transcriptionfactorHEY1inglioblastoma.JCellMolMed,2009, 13(1):136-146.
[12] Yu H, Jia R, Zhao L, et al. LDB2 inhibits proliferation and migration in liver cancer cells by abrogating HEY1 expression. Oncotarget, 2017, 8(55):94440-94449.
[13]李维,刘旭,张国倩,等.动物水平的绿原酸通过Notch1信号通路调控非小细胞肺癌凋亡及机制研究.中国肺癌杂志, 2017, 20(8):555-561.
[14] Konishi J, Kawaguchi KS, Vo H, et al. Gamma-secretase inhibitor prevents Notch3 activation and reduces proliferation inhumanlungcancers.CancerRes,2007,67(17):8051-8057.
[15] Galluzzo P, Bocchetta M. Notch signaling in lung cancer.Expert Rev Anticancer Ther, 2011, 11(4):533-540.
[16]姜昕,周建华,邓征浩,等. Notch1,Jagged1和VEGF蛋白在非小细胞肺癌的表达及其意义.中南大学学报(医学版),2007,32(6):1031-1036.
[17]李钰泉,周天骏,潘越江,等. Notch1和Notch3在非小细胞肺癌组织中的表达及其意义.中华实验外科杂志,2013,30(12):2714-2716.
[18] Huang J, Song H, Liu B, et al. Expression of Notch-1 and its clinical significance in different histological subtypes of human lung adenocarcinoma. J Exp Clin Cancer Res, 2013,32:84.
[19] Kamat AA,FletcherM,GrumanLM,etal. Theclinical relevance of stromal matrix metalloproteinase expression in ovarian Cancer. Clin Cancer Res, 2006, 12(6):1707-1714.
[20] Weber D, Wiese C, Gessler M. Hey bHLH transcription factors. Curr Top Dev Biol, 2014, 110:285-315.
[21] Heisig J, Weber D, Englberger E, et al. Target gene analysis by microarrays and chromatin immunoprecipitation identifiesHEY proteins as highly redundant bHLH repressors.PLoS Genet, 2012, 8(5):e1002728.
[22] HouJ, AertsJ,HamerBD,etal.Geneexpression-based classification of non-small cell lung carcinomas and survival prediction. PLoS One, 2010, 5(4):e10312.
[23] Wang XM, Song N, Zhang Y, et al. Coexpression of c-Met and Notch-1 correlates with poor prognosis in resected nonsmall-celllungcancer. TumourBiol,2015,36(9):7053-7059.
[24] Liu ZY, Wu T, Li Q, et al. Notch Signaling Components:-Diverging Prognostic Indicators in Lung Adenocarcinoma.Medicine(Baltimore), 2016, 95(20):e3715.
[2]Bernhardt M, Galach M, Novak D, et al. Mediators of induced pluripotency and their role in cancer cells-current scientific knowledge and future perspectives. Biotechnol J,2012, 7(6):810-821.
[3]Zanotti S, Canalis E. Notch and the skeleton. Mol Cell Biol,2010, 30(4):886-896.
[4]Leong KG, Karsan A. Recent insights into the role of Notch signaling in tumorigenesis. Blood, 2006, 107(6):2223-2233.
[5]Liu TJ, Gao YH, Sakamoto K. BMP-2 Promotes Differentiation of Osteoblasts and Chondroblasts in Runx2-Deficient Cell Lines. J Cell Physiol, 2007, 211(3):728-735.
[6]Camilla D, Andries B, Gavin C. Functional Notch signaling is required for BMP4-induced inhibition of myogenic differentiation. Development, 2003, 130(24):6089-6099.
[7]Tsuru A, Setoguchi T, Matsunoshita Y, et al. Hairy/enhancerof-split related with YRPW motif protein 1 promotes osteosarcoma metastasis via matrix metallopeptidase 9 expression. Br J Cancer, 2015, 112(7):1232-1240.
[8]Candy PA, Phillips MR, Redfern AD, et al. Notch-induced transcription factors are predictive of survival and 5-fluorouracil response in colorectal cancer patients. Br J Cancer,2013, 109(4):1023-1030.
[9]Mann CD, Bastianpillai C, Neal CP, et al. Notch3 and HEY-1 as prognostic biomarkers in pancreatic adenocarcinoma.PLoS One, 2012, 7(12):e51119.
[10] Jung CW, Kong JS, Seol H, et al. Expression of activated Notch1 and Hey1 in papillary thyroid carcinoma. Histopathology, 2017, 70(2):301-308.
[11] Hulleman E, Quarto M, Vernell R, et al. A role for the transcriptionfactorHEY1inglioblastoma.JCellMolMed,2009, 13(1):136-146.
[12] Yu H, Jia R, Zhao L, et al. LDB2 inhibits proliferation and migration in liver cancer cells by abrogating HEY1 expression. Oncotarget, 2017, 8(55):94440-94449.
[13]李维,刘旭,张国倩,等.动物水平的绿原酸通过Notch1信号通路调控非小细胞肺癌凋亡及机制研究.中国肺癌杂志, 2017, 20(8):555-561.
[14] Konishi J, Kawaguchi KS, Vo H, et al. Gamma-secretase inhibitor prevents Notch3 activation and reduces proliferation inhumanlungcancers.CancerRes,2007,67(17):8051-8057.
[15] Galluzzo P, Bocchetta M. Notch signaling in lung cancer.Expert Rev Anticancer Ther, 2011, 11(4):533-540.
[16]姜昕,周建华,邓征浩,等. Notch1,Jagged1和VEGF蛋白在非小细胞肺癌的表达及其意义.中南大学学报(医学版),2007,32(6):1031-1036.
[17]李钰泉,周天骏,潘越江,等. Notch1和Notch3在非小细胞肺癌组织中的表达及其意义.中华实验外科杂志,2013,30(12):2714-2716.
[18] Huang J, Song H, Liu B, et al. Expression of Notch-1 and its clinical significance in different histological subtypes of human lung adenocarcinoma. J Exp Clin Cancer Res, 2013,32:84.
[19] Kamat AA,FletcherM,GrumanLM,etal. Theclinical relevance of stromal matrix metalloproteinase expression in ovarian Cancer. Clin Cancer Res, 2006, 12(6):1707-1714.
[20] Weber D, Wiese C, Gessler M. Hey bHLH transcription factors. Curr Top Dev Biol, 2014, 110:285-315.
[21] Heisig J, Weber D, Englberger E, et al. Target gene analysis by microarrays and chromatin immunoprecipitation identifiesHEY proteins as highly redundant bHLH repressors.PLoS Genet, 2012, 8(5):e1002728.
[22] HouJ, AertsJ,HamerBD,etal.Geneexpression-based classification of non-small cell lung carcinomas and survival prediction. PLoS One, 2010, 5(4):e10312.
[23] Wang XM, Song N, Zhang Y, et al. Coexpression of c-Met and Notch-1 correlates with poor prognosis in resected nonsmall-celllungcancer. TumourBiol,2015,36(9):7053-7059.
[24] Liu ZY, Wu T, Li Q, et al. Notch Signaling Components:-Diverging Prognostic Indicators in Lung Adenocarcinoma.Medicine(Baltimore), 2016, 95(20):e3715.