宫颈癌组织中Toll样受体9和干扰素调节因子7蛋白表达与人乳头状瘤病毒感染的关系
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摘要
目的探讨子宫颈病变中Toll样受体9(TLR9)和干扰素调节因子7(IRF7)表达与人类乳头状病毒16(HPV16)感染的关系。方法以HPV-GenoCam-9600检测46例宫颈癌,25例高级别鳞状上皮内病变(HSIL)和23例慢性宫颈炎组织HPV感染及分型;采用Illumina Hiseq 4000测序平台对15例宫颈病变组织进行转录组测序;通过免疫组化SP法检测TLR9和IRF7在慢性宫颈炎、HSIL和宫颈癌患者石蜡包埋组织中的表达水平。结果HPV基因芯片分析结果显示,在94例HPV阳性的标本中共检测到11个HPV基因型,在66例宫颈癌及癌前期病变中的10例为多重感染,多重感染率为15.1%(10/66)。3例HPV阳性的慢性宫颈炎组织中都是HPV16阳性。12个HPV基因型中高危型为10个,低危型2个。转录组测序结果显示,HPV16阳性的宫颈癌和HSIL组织中与TLR9相关的差异上调表达的基因有12个;免疫组织化学结果显示TLR9和IRF7在HSIL和宫颈癌组织中高表达,其表达水平呈正相关(P<0.05),但TLR9在HPV16阳性的宫颈病变组织中表达低于HPV16阴性的宫颈病变组织,且与IRF7蛋白表达呈正相关。结论 TLR9和IRF7蛋白参与了子宫颈癌发生发展,但具体调控机制需要深入研究。
Objective To investigate the relationship between the expression of Toll like receptor 9(TLR9)and interferon regulatory factor 7(IRF7)and human papillomavirus16(HPV16)infection in female cervical lesions.Methods 94 cases of cervical cancer were detected by hpv-genocam-9600 to diagnose as 46 cased of cervical carcinoma,25 cases of high grade squamous intraepithelial lesions and 23 cases of chronic cervicitis;Illumina Hiseq 4000 sequen HSILg platform was used to sequence the transcriptome of 15 cases of cervical lesions.The expression of TLR9 and IRF7 in the paraffin embedded tissue of chronic cervicitis and cervical cancer was detected by immunohistochemical SP method.Results The results of HPV gene chip analysis showed that 11 HPV genotypes were detected in 86 HPV positive specimens and 10 of 66 cervical cancer and precancerous lesions were multiple infections.The multiple infection rate was 15.10%(10/66).3 cased of HPV positive in chronic cervitis tissues were all HPV16 positive,and 10 of the 12 HPV genotypes were high-risk,and 2 were low-risk.The results of transcriptome sequenHSILg showed that there were 12 differentially expressed genes related to TLR9 in cervical carHSILoma and HSIL.Immunohistochemical results showed that TLR9 and IRF7 were highly expressed in HSIL and cervical cancer tissues,and the correlation between the expression levels of HSIL and IRF7 was positive(P <0.05).However,the expression of TLR9 in HPV16 positive cervical lesions was lower than that in HPV16 negative cervical lesions,and with positive correlation to IRF7 protein.Conclusion The expression of TLR9 and IRF7 protein may be involved in the occurrence and development of cervical cancer in women.But the specific regulatory mechanisms need to be further studies.
Objective To investigate the relationship between the expression of Toll like receptor 9(TLR9)and interferon regulatory factor 7(IRF7)and human papillomavirus16(HPV16)infection in female cervical lesions.Methods 94 cases of cervical cancer were detected by hpv-genocam-9600 to diagnose as 46 cased of cervical carcinoma,25 cases of high grade squamous intraepithelial lesions and 23 cases of chronic cervicitis;Illumina Hiseq 4000 sequen HSILg platform was used to sequence the transcriptome of 15 cases of cervical lesions.The expression of TLR9 and IRF7 in the paraffin embedded tissue of chronic cervicitis and cervical cancer was detected by immunohistochemical SP method.Results The results of HPV gene chip analysis showed that 11 HPV genotypes were detected in 86 HPV positive specimens and 10 of 66 cervical cancer and precancerous lesions were multiple infections.The multiple infection rate was 15.10%(10/66).3 cased of HPV positive in chronic cervitis tissues were all HPV16 positive,and 10 of the 12 HPV genotypes were high-risk,and 2 were low-risk.The results of transcriptome sequenHSILg showed that there were 12 differentially expressed genes related to TLR9 in cervical carHSILoma and HSIL.Immunohistochemical results showed that TLR9 and IRF7 were highly expressed in HSIL and cervical cancer tissues,and the correlation between the expression levels of HSIL and IRF7 was positive(P <0.05).However,the expression of TLR9 in HPV16 positive cervical lesions was lower than that in HPV16 negative cervical lesions,and with positive correlation to IRF7 protein.Conclusion The expression of TLR9 and IRF7 protein may be involved in the occurrence and development of cervical cancer in women.But the specific regulatory mechanisms need to be further studies.
引文
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[4]蔡玉群,李薇,万惠卿,等.2010-2012年杭州市拱墅区已婚育龄妇女宫颈癌筛查结果分析[J].中国肿瘤,2014,23(9):752-756.
[5]吕倩灵,张玲,林伟平.高危型人乳头状瘤病毒及病毒载量对宫颈癌癌前病变的相关性分析[J].中华医院感染学杂志,2014,24(4):804-805.
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[7]阿仙姑·哈斯木,李巧稚,马俊旗,等.维吾尔族患者宫颈病变中内质网分子伴侣和HLA-Ⅰ类分子表达与HPV16感染的关系研究[J].实用妇产科杂志,2011,27(2):102-105.
[8]ALEMANY L,DE SANJOSS,TOUS S,et al.Tim etrends of human papillom a-virus types in invasive cervical cancer,from 1940to 2007[J].Int J Cancer,2014,135(1):88-95.
[9]CANNELLA F,PIERANGELI A,SCAGNOLARI C,et al.TLR9is expressed in human papillomavirus-positive cervical cells and is overexpressed in persistent infections[J].Immunobiology,2014,220(3):363-368.
[10]LAI Z Z,NIZHANG,PAN X L,et al.Toll-like receptor 9(TLR9)gene polymorphisms associated with increased susceptibility of human papillomavirus-16infection in patients with cervical cancer[J].J Int Med Res,2013,41(4):1027.
[11]CHANG L C,FAN C W,TSENG W K,et al.IFNAR1is a predictor for overall survival in colorectal cancer and its mRNA expression correlated with IRF7but not TLR9[J].MediHSILe,2014,93(29):e349.
[12]李恩亮,邬林泉.干扰素调节因子7与肿瘤关系研究进展[J].国际外科学杂志,2017,44(1):60-63.
[13]BIDWELL B N,SLANEY C Y,WITHANA N P,et al.SilenHSILg of Irf7pathways in breast cancer cells promotes bone metastasis through immune escape[J].Nature Med,2012,18(8):1224-1231.
[2]齐月,金清龙,温晓玉,等.肝细胞中固有干扰素调节因子7的表达及其抗病毒作用[J].吉林大学学报(医学版),2012,38(2):183-186.
[3]阿仙姑·哈斯木.维吾尔族宫颈癌发生与抗原呈递元件基因表达调控的关系研究[D].乌鲁木齐:新疆医科大学,2011.
[4]蔡玉群,李薇,万惠卿,等.2010-2012年杭州市拱墅区已婚育龄妇女宫颈癌筛查结果分析[J].中国肿瘤,2014,23(9):752-756.
[5]吕倩灵,张玲,林伟平.高危型人乳头状瘤病毒及病毒载量对宫颈癌癌前病变的相关性分析[J].中华医院感染学杂志,2014,24(4):804-805.
[6]ZHOU Q,ZHU K,CHENG H.Toll-like receptors in human papilloma-virus infection[J].Arc Immunol Ther Exp(War sz),2013,61(3):203-215.
[7]阿仙姑·哈斯木,李巧稚,马俊旗,等.维吾尔族患者宫颈病变中内质网分子伴侣和HLA-Ⅰ类分子表达与HPV16感染的关系研究[J].实用妇产科杂志,2011,27(2):102-105.
[8]ALEMANY L,DE SANJOSS,TOUS S,et al.Tim etrends of human papillom a-virus types in invasive cervical cancer,from 1940to 2007[J].Int J Cancer,2014,135(1):88-95.
[9]CANNELLA F,PIERANGELI A,SCAGNOLARI C,et al.TLR9is expressed in human papillomavirus-positive cervical cells and is overexpressed in persistent infections[J].Immunobiology,2014,220(3):363-368.
[10]LAI Z Z,NIZHANG,PAN X L,et al.Toll-like receptor 9(TLR9)gene polymorphisms associated with increased susceptibility of human papillomavirus-16infection in patients with cervical cancer[J].J Int Med Res,2013,41(4):1027.
[11]CHANG L C,FAN C W,TSENG W K,et al.IFNAR1is a predictor for overall survival in colorectal cancer and its mRNA expression correlated with IRF7but not TLR9[J].MediHSILe,2014,93(29):e349.
[12]李恩亮,邬林泉.干扰素调节因子7与肿瘤关系研究进展[J].国际外科学杂志,2017,44(1):60-63.
[13]BIDWELL B N,SLANEY C Y,WITHANA N P,et al.SilenHSILg of Irf7pathways in breast cancer cells promotes bone metastasis through immune escape[J].Nature Med,2012,18(8):1224-1231.