维吾尔族妇女宫颈癌与新一类肿瘤特异性上调表达基因调控的关系研究
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摘要
目的通过新的维吾尔族妇女宫颈癌组织特异性上调表达基因的分析,探讨宫颈癌发生与基因表达调控的关系及临床意义。方法选择6种新发现的宫颈癌组织特异性上调表达候选基因,设计mRNA特异性引物,对25例宫颈鳞癌(cervical squamous cell carcinoma,CSCC)、22例宫颈内上皮瘤变(cervical intraepithelial neoplasia,CIN)Ⅱ~Ⅲ和25例宫颈炎组织RNA进行半定量RT-PCR鉴定。结果 CSCC与宫颈炎组织比较,SHISA2、SIX1、果蝇同源盒基因(DTL)、桥粒芯糖蛋白-2(DSG2)、NUP62CL和胞嘧啶脱氨酶(APOBE63B)6种基因的mRNA水平均有差异(P<0.05);CSCC与CINⅡ~Ⅲ比较,SHISA2、SIX1、APOBEC3B和DSG2 4种基因的mRNA水平有差异(P<0.05),而CINⅡ~Ⅲ与宫颈炎比较,只有SHISA2基因的mRNA水平差异有统计学意义(P<0.05)。结论 SHISA2、SIX1、DTL、DSG2、NUP62CL和APOBE63B6种基因的转录表达水平变化可能成为维吾尔族妇女宫颈癌发生的早期预警标志物。
Objective To screen novel genes upregulated in cervical cancer,and investigate association of cervical carcinogenesis with the regulation of gene expression and clinical outcome.Methods We selected six newly identified genes specific to,and upregulated in,tissue specimens of cervical carcinoma.After designing of mRNA sequence specific primers,the expression level of these genes was detected by semi-quantitative RT-PCR,in a total of 72cases of fresh tissue specimens from Uyghur women with cervix lesions including 25cases of cervical squamous cell carcinoma(CSCC),22cases of cervical intraepithelial neoplasia(CIN)and 25cases of cervicitis or normal cervix(NC);Results The transcription levels of SHISA2, SIX1,DTL,DSG2,NUP62CL and APOBE63Bwere significantly different in CSCC from NC(P<0.05). CSCC compared to CINⅡ-Ⅲ,the expression of SHISA2,SIX1,APOBEC3Band DSG2gene were signifi-cantly different(P <0.05).Except for SHISA2,no differences were found for the expression of other genes when CINⅡ-Ⅲ and NC was compared(P >0.05).Conclusion The aberrant up-regulation of SHISA2,SIX1,DTL,DSG2,NUP62CL and APOBE63Bgene expression may become potential markers for the early diagnosis of cervical carcinoma.
Objective To screen novel genes upregulated in cervical cancer,and investigate association of cervical carcinogenesis with the regulation of gene expression and clinical outcome.Methods We selected six newly identified genes specific to,and upregulated in,tissue specimens of cervical carcinoma.After designing of mRNA sequence specific primers,the expression level of these genes was detected by semi-quantitative RT-PCR,in a total of 72cases of fresh tissue specimens from Uyghur women with cervix lesions including 25cases of cervical squamous cell carcinoma(CSCC),22cases of cervical intraepithelial neoplasia(CIN)and 25cases of cervicitis or normal cervix(NC);Results The transcription levels of SHISA2, SIX1,DTL,DSG2,NUP62CL and APOBE63Bwere significantly different in CSCC from NC(P<0.05). CSCC compared to CINⅡ-Ⅲ,the expression of SHISA2,SIX1,APOBEC3Band DSG2gene were signifi-cantly different(P <0.05).Except for SHISA2,no differences were found for the expression of other genes when CINⅡ-Ⅲ and NC was compared(P >0.05).Conclusion The aberrant up-regulation of SHISA2,SIX1,DTL,DSG2,NUP62CL and APOBE63Bgene expression may become potential markers for the early diagnosis of cervical carcinoma.
引文
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[16]Ng KT,Man K,Sun CK,et al.Clinicopathological significance of homeoprotein Six1in hepatocellular carcinoma[J].Br J Cancer,2006,95(8):1050-1055.
[17]Baraniskin A,Birkenkamp-Demtroder K,Maghnouj A,et al.MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL[J].Carcinogenesis,2012,33(4):732-739.
[18]Rasmussen TB,Palmfeldt J,Nissen PH,et al.Mutated desmoglein-2proteins are incorporated into desmosomes and exhibit dominant-negative effects in arrhythmogenic right ventricular cardiomyopathy[J].Hum Mutat,2013,34(5):697-705.
[19]Chiu YL,Greene WC.The APOBEC3cytidine deaminases:an innate defensive network opposing exogenous retroviruses and endogenous retroelements[J].Annu Rev Immunol,2008,26:317-353.
[20]阿丽叶古丽·艾皮热.西尔扎提·苏来曼,吐尔逊帕夏·吾布力卡斯木等.宫颈癌及癌前病变的全基因组表达谱分析及下调表达候选基因鉴定[J].新疆医科大学学报,2013,36(7):913-917.
[2]肿瘤早期诊断技术及标准研讨会纪要[J].中国医药导刊,2006,8(4):312.
[3]Wong YF,Cheung TH,Tsao GS,et al.Genome-wide gene expression profiling of cervical Cancer in Hong Kong women by oligonucleotide microarray[J].Cancer,2006,118(10):2461-2469.
[4]Chao A,Wang TH,Lee YS,et al.Molecular characterization of adenocarcinoma and squamous carcinoma of the uterine cervix using microarray analysis of gene expression[J].Cancer,2006,119(1):91-98.
[5]Grigsby PW,Watson M,Powell MA,et al.Gene expression patterns in advanced human cervical Cancer[J].Int J Gynecol Cancer,2006,16(2):562-567.
[6]Sunde J,Liu Y,Lu DC,et al.Endothelin-3growth factor levels decreased in cervical Cancer compared with normal cervical epithelial cells[J].Hum Pathol,2007,38(7):1047-1056.
[7]拉莱·苏祖克,彭玉华,周康,等.新疆不同民族宫颈癌发病趋势分析[J].新疆医科大学学报,2006,29(7):569-571.
[8]凌斌.子宫颈癌诊断与治疗的新进展[J].中国实用妇科与产科杂志,2007,23(1):23-25.
[9]佚名.肿瘤早期诊断技术及标准研讨会纪要[J].中国医药导刊,2006,8(4):312.
[10]刘开江,李庭芳,赵峰,等.应用基因芯片筛查维吾尔族妇女子宫颈癌相关基因[J].中华妇产科杂志,2003,38(6):325-327.
[11]Filipe M,Gonalves L,Bento M,et al.Comparative expression of mouse and chicken Shisa homologues during early development[J].Dev Dyn,2006,235(9):2567-2573.
[12]Yu Y,Khan J,Khanna C,et al.Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1as key metastatic regulators[J].Nat Med,2004,10(2):175-181.
[13]郑秀惠.Six1基因对宫颈癌细胞生物学行为的影响及其机制研究[D].重庆:第三军医大学,2010:8-10.
[14]Grier DG,Thompson A,Kwasniewska A,et al.The pathophysiology of HOX genes and their role in Cancer[J].J Pathol,2005,205(2):154-171.
[15]Coletta RD,Christensen KL,Micalizzi DS,et al.Six1overexpression in mammary cells induces genomic instability and is sufficient for malignant transformation[J].Cancer Res,2008,68(7):2204-2213.
[16]Ng KT,Man K,Sun CK,et al.Clinicopathological significance of homeoprotein Six1in hepatocellular carcinoma[J].Br J Cancer,2006,95(8):1050-1055.
[17]Baraniskin A,Birkenkamp-Demtroder K,Maghnouj A,et al.MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL[J].Carcinogenesis,2012,33(4):732-739.
[18]Rasmussen TB,Palmfeldt J,Nissen PH,et al.Mutated desmoglein-2proteins are incorporated into desmosomes and exhibit dominant-negative effects in arrhythmogenic right ventricular cardiomyopathy[J].Hum Mutat,2013,34(5):697-705.
[19]Chiu YL,Greene WC.The APOBEC3cytidine deaminases:an innate defensive network opposing exogenous retroviruses and endogenous retroelements[J].Annu Rev Immunol,2008,26:317-353.
[20]阿丽叶古丽·艾皮热.西尔扎提·苏来曼,吐尔逊帕夏·吾布力卡斯木等.宫颈癌及癌前病变的全基因组表达谱分析及下调表达候选基因鉴定[J].新疆医科大学学报,2013,36(7):913-917.