Fas、cFLIP及TGF-β_1在宫颈鳞癌组织中的表达及意义
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摘要
目的研究凋亡相关因子(Fas)、细胞型Fas相关死亡结构域蛋白样白介素-1β转换酶抑制蛋白(cFLIP)及转化生长因子β_1(TGF-β_1)在正常宫颈组织、宫颈上皮内瘤变组织和宫颈鳞癌组织中的表达,以及与宫颈鳞癌临床病理和分期的关系,探讨3者在宫颈鳞癌发生、发展中的作用,同时也为寻找宫颈癌的诊断和治疗新靶点提供理论依据。方法采用免疫组织化学法检测59例宫颈鳞癌、45例子宫颈上皮内瘤变(CIN)和15例正常宫颈组织中cFLIP、Fas及TGF-β_1的表达,并进行相关临床病理因素分析。结果在宫颈病变由良性到恶性的发展过程中,Fas和TGF-β_1的表达水平逐渐降低(P<0.05),cFLIP的表达水平逐渐升高(P<0.05)。在宫颈鳞癌发展过程中,Fas与cFLIP表达呈负相关(P<0.05),Fas与TGF-β_1的表达呈正相关(P<0.05)。结论Fas、TGF-β_1表达下调,以及cFLIP表达上调在宫颈鳞癌的发生、发展中发挥重要作用。
Objective To study the expressions of factor associated suicide(Fas), cellular Fas-associated death domain-like interleukin-lβ-converting enzyme(FLICE)-like inhibitory protein(cFLIP) and transforming growth factor-β(TGF-β_1) in the tissues of normal cervix, cervical intraepithelial neoplasia(CIN) and cervical squamous carcinoma as well as their relationships with the clinical pathology and staging of cervical squamous carcinoma, and explore their roles in the occurrence and development of cervical squamous carcinoma, so as to provide certain theoretical evidence for seeking a new target of diagnosis and treatment of cervical squamous cancer. Methods Immunohistochemical staining was used to examine the expressions of Fas, cFLIP and TGF-β_1 in different cervical tissues. Their relationships with clinicopathological factors were analyzed. Results From the normal cervical tissues, CIN to cervical squamous carcinoma, the expression levels of Fas and TGF-β_1 gradually decreased(P < 0.05), and cFLIP expression gradually increased(P < 0.05). There was a closely negative correlation between Fas and cFLIP expressions(P < 0.05), and a positive correlation between Fas and TGF-β_1 expressions(P < 0.05) in the development of cervical squamous carcinoma. Conclusions Down-regulation of Fas and TGF-β_1 expressions and up-regulation of cFLIP expression play important roles in the development of cervical squamous carcinoma.
Objective To study the expressions of factor associated suicide(Fas), cellular Fas-associated death domain-like interleukin-lβ-converting enzyme(FLICE)-like inhibitory protein(cFLIP) and transforming growth factor-β(TGF-β_1) in the tissues of normal cervix, cervical intraepithelial neoplasia(CIN) and cervical squamous carcinoma as well as their relationships with the clinical pathology and staging of cervical squamous carcinoma, and explore their roles in the occurrence and development of cervical squamous carcinoma, so as to provide certain theoretical evidence for seeking a new target of diagnosis and treatment of cervical squamous cancer. Methods Immunohistochemical staining was used to examine the expressions of Fas, cFLIP and TGF-β_1 in different cervical tissues. Their relationships with clinicopathological factors were analyzed. Results From the normal cervical tissues, CIN to cervical squamous carcinoma, the expression levels of Fas and TGF-β_1 gradually decreased(P < 0.05), and cFLIP expression gradually increased(P < 0.05). There was a closely negative correlation between Fas and cFLIP expressions(P < 0.05), and a positive correlation between Fas and TGF-β_1 expressions(P < 0.05) in the development of cervical squamous carcinoma. Conclusions Down-regulation of Fas and TGF-β_1 expressions and up-regulation of cFLIP expression play important roles in the development of cervical squamous carcinoma.
引文
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[16]程时丹,王晓瑾,乔敏敏,等.Smad4基因抑制人类胃癌细胞株生长的作用机制[J].上海交通大学学报(医学版),2007,27(5):546-551.
[2]邢传平,刘斌,董亮,免疫组织化学标记结果的判断方法[J].中华病理学杂志,2001,30(4):318.
[3]IWASE M,KONDO G,WANTANABE H,et al.Regulation of fas-mediate apoptosis in neutrophils after surgery induced acute inflammation[J].J Surg Res,2006,134(1):114-123.
[4]DAS H,KOIZUMI T,SUGIMOTO T,et al.Quantitation of Fas and Fas ligand gene expression in human ovarian,cervical and endometrial carcinomas using real-time quantitative RT-PCR[J].Br J Cancer,2000,82(10):1682-1688.
[5]王娟,王薇,罗爱月.Fas、FasL及cF LIP在宫颈病变中的表达与宫颈癌发生、发展相关性的初步探讨[J].中国癌症杂志,2007,17(9):674-678.
[6]IRMLER M,THOME M,HAHNE M,et al.Inhibition of death receptor signals by celluar FLIP[J].Nature,1997,388(6638):190-195.
[7]VALENTE G,MANEROI F,PERACCHIO C,et al.cF LIP expression correlates with tumour progression and patient outcome in non-Hodgkin lymphomas of low grade of malignancy[J].Br JHaematol,2006,132(5):560-570.
[8]RYU B K,LEE M G,CHI S G,et al.Increased expression of cF LIP(L)in colonic adenocarcinoma[J].J Pathol,2001,194(1):15-19.
[9]THOMAS R K,KALLENBORN A,WICKENHAUSER C,et al.Constitutive expressionof cF LIP in hodgkin and reed-sternberg cells[J].Am J Pathol,2002,160(4):1521-1528.
[10]张颖奇,李华,徐波,等.cF LIP、TBX2在颅内外鳞癌中的表达及意义[J].中国实用神经疾病杂志,2014,17(10):100-101.
[11]HAZELBAG S,KENTER G G,GORTER A,et al.Prognostic relevance of TGF-beta1 and PAI-1 in cervical cancer[J].Int JCancer,2004,112(6):1020-1028.
[12]XIONG B,GONG L L,ZHANG F,et al.TGF beta1 expression and angiogenesis in colorectal cancer tissue[J].World J Gastroenterol,2002,8(3):496-498.
[13]王春雷,黄志强,万远廉,等.TGF-β诱导人肝癌细胞系凋亡信号转导机理的研究[J].中国普外基础与临床杂志,2005,12(5):480-482.
[14]PETER M E,KRAMMER P H.The CD95(APO-1/Fas)DISCand beyond[J].Cell Death Differ,2003,10(1):26-35.
[15]BADAWI A F,EL-SOHEMY A,STEPHEN L L,et al.The effect of dietary polyunsaturated fatty acids on the expression of cyclooxygenase 1 and 2 and levels of p21 ras in rat mammary glands[J].Carcinogenesis,1998,19(5):905-910.
[16]程时丹,王晓瑾,乔敏敏,等.Smad4基因抑制人类胃癌细胞株生长的作用机制[J].上海交通大学学报(医学版),2007,27(5):546-551.