ARTN在食管鳞状细胞癌中的表达及临床病理联系
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摘要
目的:研究ARTN在食管鳞状细胞癌组织中的表达及与食管鳞癌患者临床病理特征及预后的联系。方法:采用免疫组化SP两步法检测ARTN蛋白在114例食管鳞状细胞癌组织、17例高级别上皮内瘤变组织、25例正常食管组织中的表达;Western blot法检测ARTN在12例新鲜食管鳞癌组织及配对的癌旁组织中的表达,分析ARTN表达与患者临床病理及预后的关系。结果:免疫组化:ARTN在食管正常组织、高级别上皮内瘤变组织、食管鳞癌组织中的阳性表达率分别为0%(0/25)、23.5%(6/17)、80.7%(92/114);Western blot:食管鳞癌组织中ARTN的表达高于癌旁正常组织。结论:ARTN表达与癌浸润深度、TNM分期及预后相关(P<0.01),可能成为判断患者浸润深度、临床分期及预后的指标。
Objective:To investigate the expression as well as its clinical and prognostic significance of ARTN in esophagus squamous cell carcinoma(ESCC).Methods:114 cases of esophagus squamous cell carcinoma,17 cases of high grade intraepithelial neoplasia and 25 cases of nomal esophageal tissue were selected to determine the expression of ARTN by immunohistochemistry.12 cases of fresh tissues and paired nomal tissues were selected to determine the expression of ARTN by Western-blot.The relationship between ARTN expression and clinical pathology and prognosis was analyzed.Results:The percentage of positive expression of ARTN in nomal esophageal tissue,high grade intraepithelial tissue and ESCC were 0,23.5%,80.7% respectively by immunohistochemistry,and the expression of ARTN in ESCC was higher than that in adjacent normal tissues by Western blot.Conclusion:The expression of ARTN is correlated with the depth of invasion,TNM stage and prognosis of cancer(P<0.01),which may be an index to judge the depth of invasion,clinical stage and prognosis of patients.
Objective:To investigate the expression as well as its clinical and prognostic significance of ARTN in esophagus squamous cell carcinoma(ESCC).Methods:114 cases of esophagus squamous cell carcinoma,17 cases of high grade intraepithelial neoplasia and 25 cases of nomal esophageal tissue were selected to determine the expression of ARTN by immunohistochemistry.12 cases of fresh tissues and paired nomal tissues were selected to determine the expression of ARTN by Western-blot.The relationship between ARTN expression and clinical pathology and prognosis was analyzed.Results:The percentage of positive expression of ARTN in nomal esophageal tissue,high grade intraepithelial tissue and ESCC were 0,23.5%,80.7% respectively by immunohistochemistry,and the expression of ARTN in ESCC was higher than that in adjacent normal tissues by Western blot.Conclusion:The expression of ARTN is correlated with the depth of invasion,TNM stage and prognosis of cancer(P<0.01),which may be an index to judge the depth of invasion,clinical stage and prognosis of patients.
引文
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[2] Hui Li,Fang WT,Yu ZT,et al.Chinese expert consensus on mediastinal lymph node dissection in esophagectomy for esophageal cancer (2017 edition) [J].J Thorac Dis,2018,10(4):2481-2489.
[3] Fernandez RM,Ruiz-Ferrer M,Lopez-Alonso M,et al.Polymorphisms in the genes encoding the 4 RET ligands,GDNF,NTN,ARTN,PSPN,and susceptibility to Hirschsprung disease[J].J Pediatr Surg,2008,43(11):2042-2047.
[4] Baloh RH,Tansey MG,Lampe PA,et al.Artemin,a novel member of the GDNF ligand family,supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex[J].Neuron,1998,21(6):1291-1302.
[5] Lin DC,Wang MR,Koeffler HP.Genomic and Epigenomic Aberrations in Esophageal Squamous Cell Carcinoma and Implications for Patients[J].Gastroenterology,2018,154(2):374-389.
[6] Wang CN,Wang JN,Chen ZL,et al.Immunohistochemical prognostic markers of esophageal squamous cell carcinoma:a systematic review[J].Chin J Cancer,2017,36(1):65-82.
[7] Kashyap MK,Abdel-Rahman O.Expression,regulation and targeting of receptor tyrosine kinases in esophageal squamous cell carcinoma[J].Mol Cancer,2018,17(1):54-65.
[8] Sgourakis G,Gockel I,Lang H.Endoscopic and surgical resection of T1a/T1b esophageal neoplasms:a systematic review[J].World J Gastroenterol,2013,19(9):1424-1437.
[9] Pandey V,Jung YW,Kang J,et al.Artemin Reduces Sensitivity to Doxorubicin and Paclitaxel in Endometrial Carcinoma Cells through Specific Regulation of CD24[J].Transl Oncol,2010,3(4):218-229.
[10] Banerjee A,Qian PX,Wu ZS,et al.Artemin stimulates radio-and chemo-resistance by promoting TWIST1-BCL-2-dependent cancer stem cell-like behavior in mammary carcinoma cells[J].J Biol Chem,2012,287(51):42502-42515.
[11] Ding KS,Banerjee A,Tan S,et al.Artemin,a member of the glial cell line-derived neurotrophic factor family of ligands,is HER2-regulated and mediates acquired trastuzumab resistance by promoting cancer stem cell-like behavior in mammary carcinoma cells[J].J Biol Chem,2014,289(23):16057-16071.
[12] Gao CB,Cheng XW,Li XH,et al.Prognostic significance of artemin and GFRalpha1 expression in laryngeal squamous cell carcinoma[J].Exp Ther Med,2014,8(3):818-822.
[13] Song ZQ,Yang F,Du H,et al.Role of artemin in non-small cell lung cancer[J].Thorac Cancer,2018,9(5):555-562.
[14] Li SJ,Li ZG,Guo FJ,et al.miR-223 regulates migration and invasion by targeting Artemin in human esophageal carcinoma[J].J Biomed Sci,2011,18:24.
[15] 张晶晶,范开席.ARTN、VEGF蛋白在胃癌组织中的表达及意义[J].山东医药,2012,52(45):1-3.
[16] Zhang M,Zhang WJ,Wu ZS,et al.Artemin is hypoxia responsive and promotes oncogenicity and increased tumor initiating capacity in hepatocellular carcinoma[J].Oncotarget,2016,7(3):3267-3282.
[17] 高莉.神经营养因子Artemin在胰腺癌侵袭转移中的作用[D].上海:第二军医大学,2012.
[18] May CD,Sphyris N,Evans KW,et al.Epithelial-mesenchymal transition and cancer stem cells.A dangerously dynamic duo in breast cancer progression[J].Breast Cancer Res,2011,13(1):202-211.
[19] Banerjee A,Wu ZS,Qian P,et al.Artemin synergizes with TWIST1 to promote metastasis and poor survival outcome in patients with ER-negative mammary carcinoma[J].Breast Cancer Res,2011,13(6):112-131.
[20] 缪锦峰,吴仟,曹磊,等.GDNF和ARTN及其受体与消化系统肿瘤嗜神经侵袭的关系[J].癌变·突变·畸变,2015,27(1):68-69.