神经调节蛋白1在食管癌中的表达及临床意义
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摘要
目的探讨神经调节蛋白1(neureglin1,NRG1)在食管癌组织中的表达,并分析其与临床病理特征之间的关系。方法采用免疫印迹(Western Blot)、实时荧光定量聚合酶链式反应(real-time PCR)检测食管癌及正常食管组织中NRG1在蛋白水平及核酸水平的表达,采用免疫组化(ICH)SP法检测NRG1在食管癌组织中的表达强度,并分析NRG1的表达和临床特征之间的关系。结果在蛋白水平,NRG1在食管癌组织中的表达均低于正常食管组织(P<0.05),在核酸水平也显示该趋势(P<0.05),且表达与患者的性别和肿瘤分化程度相关(P均<0.05),与年龄、吸烟、饮酒、淋巴结转移、TNM分期无相关性(P>0.05)。结论食管癌的发生及恶性程度可能与NRG1的表达相关,NRG1有可能成为食管癌治疗的新的有效靶点。
Objective To study the expression and clinical significance of neureglin1( NRG1) in esophageal carcinoma tissues. Methods The expression of NRG1 at the protein levels 1 in esophageal cancer tissue and normal esophageal tissue was detected by Western blot and at nucleic acid level by real-time quantity PCR.The relationship between the expression of NRG1 in esophageal carcinoma and clinical characteristics by Immunohistochemistry( IHC) was also analyzed. Results The expression of NRG1 at the protein level in esophageal cancer was significantly lower than both normal esophageal tissue( P < 0. 05) and at the nucleic acid level( P< 0. 05),and its expression was gender-related differentiation,but not significantly associated with with age,smoking and drinking history,lymph node metastasis and TNM stage. Conclusion The occurrence and malignancy degree of esophageal cancer may be associated with the expression of NRG1,and NRG1 may serve as a new effective target of esophageal cancer treatment.
Objective To study the expression and clinical significance of neureglin1( NRG1) in esophageal carcinoma tissues. Methods The expression of NRG1 at the protein levels 1 in esophageal cancer tissue and normal esophageal tissue was detected by Western blot and at nucleic acid level by real-time quantity PCR.The relationship between the expression of NRG1 in esophageal carcinoma and clinical characteristics by Immunohistochemistry( IHC) was also analyzed. Results The expression of NRG1 at the protein level in esophageal cancer was significantly lower than both normal esophageal tissue( P < 0. 05) and at the nucleic acid level( P< 0. 05),and its expression was gender-related differentiation,but not significantly associated with with age,smoking and drinking history,lymph node metastasis and TNM stage. Conclusion The occurrence and malignancy degree of esophageal cancer may be associated with the expression of NRG1,and NRG1 may serve as a new effective target of esophageal cancer treatment.
引文
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[18]BUAC K,XU M,CRONIN J,et al.NRG1/ERBB3 signaling in melanocyte development and melanoma:inhibition of differentiation and promotion of proliferation[J].Pigment Cell Melanoma Res,2009,22(6):773
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[3]OKUMURA H,UCHIKADO Y,SETOYAMA T,et al.Biomarkers for predicting the response of esophageal squamous cell carcinoma to neoadjuvant chemoradiation therapy[J].Surg Today,2014,44(3):421
[4]陈勃,董忠谊,曹传辉,等.蛋白激酶CK2β在食管癌中的表达及其临床意义[J].南方医科大学学报,2012,32(10):1491
[5]MONTERO J C,RODRGUEZ-BARRUECO R,OCAA A,et al.Neuregulins and cancer[J].Clin Cancer Res,2008,14(11):3237
[6]TORRE L A,BRAY F,SIEGEL R L,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87
[7]FALLS D L.Neuregulins:functions,forms,and signaling strategies[J].Exp Cell Res,2003,284(1):14
[8]ESPER R M,PANKONIN M S,LOEB J A.Neuregulins:versatile growth and differentiation factors in nervous system development and human disease[J].Brain Res Rev,2006,51(2):161
[9]MEI L,XIONG W C.Neuregulin 1 in neural development,synaptic plasticity and schizophrenia[J].Nat Rev Neurosci,2008,9(6):437
[10]TSAI M S,SHAMON-TAYLOR L A,MEHMI I,et al.Blockage of heregulin expression inhibits tumorigenicity and metastasis of breast cancer[J].Oncogene,2003,22(5):761
[11]BUONANNO A,FISCHBACH G D.Neuregulin and Erb B receptor signaling pathways in the nervous system[J].Curr Opin Neurobiol,2001,11(3):287
[12]AMIN D N,TUCK D,STERN D F.Neuregulin-regulated gene expression in mammary carcinoma cells[J].Exp Cell Res,2005,309(1):12
[13]LI W,PARK J W,NUIJENS A,et al.Heregulin is rapidly translocated to the nucleus and its transport is correlated with c-myc induction in breast cancer cells[J].Oncogene,1996,12(11):2473
[14]BIRNBAUM D,ADLADE J,POPOVICI C,et al.Chromosome arm 8p and cancer:a fragile hypothesis[J].Lancet Oncol,2003,4(10):639
[15]POLE J C,COURTAY-CAHEN C,GARCIA M J,et al.High-resolution analysis of chromosome rearrangements on8p in breast,colon and pancreatic cancer reveals a complex pattern of loss,gain and translocation[J].Oncogene,2006,25(41):5693
[16]MEETZE K,VINCENT S,TYLER S,et al.Neuregulin 1expression is a predictive biomarker for response to AV-203,an ERBB3 inhibitory antibody,in human tumor models[J].Clin Cancer Res,2015,21(5):1106
[17]LIU J,KERN J A.Neuregulin-1 activates the JAK-STAT pathway and regulates lung epithelial cell proliferation[J].Am J Respir Cell Mol Biol,2002,27(3):306
[18]BUAC K,XU M,CRONIN J,et al.NRG1/ERBB3 signaling in melanocyte development and melanoma:inhibition of differentiation and promotion of proliferation[J].Pigment Cell Melanoma Res,2009,22(6):773
[19]HASKINS J W,NGUYEN D X,STERN D F.Neuregulin1-activated ERBB4 interacts with YAP to induce Hippo pathway target genes and promote cell migration[J].Sci Signal,2014,7(355):116
[20]YEN L,YOU X L,AL MOUSTAFA A E,et al.Heregulin selectively upregulates vascular endothelial growth factor secretion in cancer cells and stimulates angiogenesis[J].Oncogene,2000,19(31):3460
[21]YAO J,XIONG S,KLOS K,et al.Multiple signaling pathways involved in activation of matrix metalloproteinase-9(MMP-9)by heregulin-β1 in human breast cancer cells[J].Oncogene,2001,20(56):8066