组织microRNA-124表达及HPV18病毒载量与宫颈癌发病的相关性
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摘要
目的探讨组织中高危型HPV病毒的载量和micro RNA-124表达水平与宫颈癌发病的相关性,为宫颈癌的临床监测以及诊断提供依据。方法选取在2013年9月-2016年9月在我院行宫颈活检的宫颈癌变患者205例,其中正常或炎症56例,宫颈上皮内瘤变Ⅰ级(cervical intraepithelial neoplasia gradeⅠ,CINⅠ)32例,宫颈上皮内瘤变Ⅱ级(CINⅡ)37例,宫颈上皮内瘤变Ⅲ级(CINⅢ)31例,宫颈癌49例(宫颈鳞癌38例,宫颈腺癌11例)。对宫颈组织或细胞采用逆转录—荧光定量PCR检测micro RNA-124的相对表达,采用第二代杂交捕获技术(HCⅡ)检测HPV18病毒的载量,病毒载量1 pg/ml为阴性组,1~50 pg/ml为低级载量组,51~500 pg/ml为中级载量组,501~1 000 pg/ml则为高级载量组,1 001 pg/ml及以上为极高病毒载量组。Spearman相关性分析病毒载量与宫颈组织病变程度的相关性。结果宫颈癌组HPV18病毒载量及micro RNA-124表达水平显著高于其他组(P均<0.05),而正常或炎症组高危型HPV病毒载量及micro RNA-124的表达水平最低(P=0.001),并且随着宫颈癌病变加重,HPV病毒载量及micro RNA-124的表达水平也随之升高;Spearman相关分析显示,高危型HPV病毒载量与宫颈病变程度呈正相关(R=0.975,P=0.000);随着宫颈癌病变加重,micro RNA-124表达水平呈线性升高(R=0.889,P=0.012)。结论宫颈组织中micro RNA-124表达水平及高危型HPV病毒载量与宫颈癌的发生密切相关。
Objective To explore the correlation of micro RNA-124 expression and high risk HPV viral load with cervical cancer so as to provide evidence for clinical monitoring and diagnosis. Methods A total of 205 patients who suffered from cervical lesions and received cervical biopsies in our hospital from September 2013 to September 2016 were included in the study. Fifty-six patients were healthy or with inflammation, 32 patients with cervical intraepithelial neoplasia grade Ⅰ (CIN Ⅰ), 37 patients with grade Ⅱ (CIN Ⅱ) and 31 patients with grade Ⅲ (CIN Ⅲ). Forty-nine patients had cervical cancer (38 cases of squamous and 11 cases of adenocarcinoma). Reverse transcription-fluorescence quantitative PCR and hybrid capture Ⅱ (HC Ⅱ) were used to detect the relative expression of micro RNA-124 and HPV18 virus load. According to the virus load, we categorized the patients into negative group (≤ 1 pg/ml), low-load group (1-50 pg/ml), medium-load group (51-500 pg/ml) and high-load group (501-1 000 pg/ml).The relationship between high risk of HPV viral load and degree of cervical tissue lesion was analyzed by Spearman analysis.Results The HPV18 virus load and level of micro RNA-124 in cervical cancer patients were significantly higher than those in other groups (all P < 0.05), while they were the lowest in the healthy and inflammation group (P =0.001). The HPV virus load and expression level of micro RNA-124 increased with the aggravation of cervical cancer. The high-risk HPV virus load was positively correlated with occurrence of cervical cancer (R =0.974, P=0.000). The expression of micro RNA-124 linearly increased with grading of cervical lesions (R =0.889, P=0.012). Conclusion The expression level of micro RNA-124 in tissues and high risk HPV virus load are closely related to cervical cancer.
Objective To explore the correlation of micro RNA-124 expression and high risk HPV viral load with cervical cancer so as to provide evidence for clinical monitoring and diagnosis. Methods A total of 205 patients who suffered from cervical lesions and received cervical biopsies in our hospital from September 2013 to September 2016 were included in the study. Fifty-six patients were healthy or with inflammation, 32 patients with cervical intraepithelial neoplasia grade Ⅰ (CIN Ⅰ), 37 patients with grade Ⅱ (CIN Ⅱ) and 31 patients with grade Ⅲ (CIN Ⅲ). Forty-nine patients had cervical cancer (38 cases of squamous and 11 cases of adenocarcinoma). Reverse transcription-fluorescence quantitative PCR and hybrid capture Ⅱ (HC Ⅱ) were used to detect the relative expression of micro RNA-124 and HPV18 virus load. According to the virus load, we categorized the patients into negative group (≤ 1 pg/ml), low-load group (1-50 pg/ml), medium-load group (51-500 pg/ml) and high-load group (501-1 000 pg/ml).The relationship between high risk of HPV viral load and degree of cervical tissue lesion was analyzed by Spearman analysis.Results The HPV18 virus load and level of micro RNA-124 in cervical cancer patients were significantly higher than those in other groups (all P < 0.05), while they were the lowest in the healthy and inflammation group (P =0.001). The HPV virus load and expression level of micro RNA-124 increased with the aggravation of cervical cancer. The high-risk HPV virus load was positively correlated with occurrence of cervical cancer (R =0.974, P=0.000). The expression of micro RNA-124 linearly increased with grading of cervical lesions (R =0.889, P=0.012). Conclusion The expression level of micro RNA-124 in tissues and high risk HPV virus load are closely related to cervical cancer.
引文
1宋晶淼,卢战凯,张晶.高危型HPV病毒载量与宫颈病变的关系[J].齐齐哈尔医学院学报,2014,35(24):3657-3658.
2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.
3郎景和.精确筛查风险分层HPV与子宫颈癌防治[J].中华妇产科杂志,2014,49(10):746-748.
4 Jin L,Xu ZX.Recent advances in the study of HPV-associated carcinogenesis[J].Virol Sin,2015,30(2):101-106.
5 Smelov V,Elfstr?m KM,Johansson ALV,et al.Long-term HPVtype-specific risks of high-grade cervical intraepithelial lesions:a14-year follow-up of a randomized primary HPV screening trial[J].Int J Cancer,2015,136(5):1171-1180.
6刘冬,叶敏娟,杨越波.HPV基因型与宫颈病变的关系探讨[J].中国肿瘤临床,2013,40(24):1531-1534.
7 Lazcano-Ponce E,Herrero R,Mu?oz N,et al.Epidemiology of HPVinfection among Mexican women with normal cervical cytology[J].Int J Cancer,2001,91(3):412-420.
8冷秀兰,范雪梅,耿建祥,等.宫颈鳞癌及腺癌组织中HPV感染基因型分布的比较研究[J].中国妇幼保健,2014,29(10):1594-1596.
9陈军莹,姚德生,贺婵娟,等.宫颈鳞癌Micro RNA差异表达的研究[J].实用医学杂志,2014,30(1):83-87.
10曾康康,莫祥兰,刘斐,等.宫颈癌及癌前病变组织中micro RNAs的差异表达[J].肿瘤防治研究,2014,41(7):789-793.
11 Quek SC,Lim BK,Domingo E,et al.Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical intraepithelial neoplasia across 5 countries in Asia[J].Int JGynecol Cancer,2013,23(1):148-156.
12王颖,刘植华.阴道乳酸杆菌与HPV感染、宫颈癌及癌前病变的相关性研究进展[J].肿瘤学杂志,2013,19(8):610-615.
13 Bhogireddy V,Roston A,Chor J,et al.Cervical intraepithelial neoplasia and cancer in women 35 years and older[J].J Low Genit Tract Dis,2014,18(1):41-45.
14马莉,丛笑,卞美璐,等.高危型HPV分型检测作为子宫颈癌及其癌前病变初筛手段的探讨[J].中华妇产科杂志,2015,50(4):246-252.
15张宗峰,杜娟.人乳头瘤病毒与微小RNA表达的相关性[J].肿瘤防治研究,2015,42(11):1152-1155.
16梁洁琼,赵敏.高危型人乳头瘤病毒整合态与宫颈上皮内瘤变及宫颈癌关系的探讨[J].中国药物与临床,2014,14(4):431-433.
17 Kang L,Zhao F,Chen F,et al.Value of high risk human papillomavirus viral load in predicting cervical lesions and triaging for high risk(HR)-HPV-positive women[J].Zhonghua Zhong Liu Za Zhi,2014,36(4):316-320.
18 Koukos G,Polytarchou C,Kaplan JL,et al.Micro RNA-124regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis[J].Gastroenterology,2013,145(4):842-852.
19苗小艳,孔繁斗,石敏,等.HPV16/18感染导致宫颈癌的分子机制研究[J].中国微生态学杂志,2015,27(10):1152-1155.
20辛婧,徐银胜,张芳,等.Micro RNA-124对人宫颈癌的抑制作用及机制研究[J].中国生物工程杂志,2015,35(10):13-19.
2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.
3郎景和.精确筛查风险分层HPV与子宫颈癌防治[J].中华妇产科杂志,2014,49(10):746-748.
4 Jin L,Xu ZX.Recent advances in the study of HPV-associated carcinogenesis[J].Virol Sin,2015,30(2):101-106.
5 Smelov V,Elfstr?m KM,Johansson ALV,et al.Long-term HPVtype-specific risks of high-grade cervical intraepithelial lesions:a14-year follow-up of a randomized primary HPV screening trial[J].Int J Cancer,2015,136(5):1171-1180.
6刘冬,叶敏娟,杨越波.HPV基因型与宫颈病变的关系探讨[J].中国肿瘤临床,2013,40(24):1531-1534.
7 Lazcano-Ponce E,Herrero R,Mu?oz N,et al.Epidemiology of HPVinfection among Mexican women with normal cervical cytology[J].Int J Cancer,2001,91(3):412-420.
8冷秀兰,范雪梅,耿建祥,等.宫颈鳞癌及腺癌组织中HPV感染基因型分布的比较研究[J].中国妇幼保健,2014,29(10):1594-1596.
9陈军莹,姚德生,贺婵娟,等.宫颈鳞癌Micro RNA差异表达的研究[J].实用医学杂志,2014,30(1):83-87.
10曾康康,莫祥兰,刘斐,等.宫颈癌及癌前病变组织中micro RNAs的差异表达[J].肿瘤防治研究,2014,41(7):789-793.
11 Quek SC,Lim BK,Domingo E,et al.Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical intraepithelial neoplasia across 5 countries in Asia[J].Int JGynecol Cancer,2013,23(1):148-156.
12王颖,刘植华.阴道乳酸杆菌与HPV感染、宫颈癌及癌前病变的相关性研究进展[J].肿瘤学杂志,2013,19(8):610-615.
13 Bhogireddy V,Roston A,Chor J,et al.Cervical intraepithelial neoplasia and cancer in women 35 years and older[J].J Low Genit Tract Dis,2014,18(1):41-45.
14马莉,丛笑,卞美璐,等.高危型HPV分型检测作为子宫颈癌及其癌前病变初筛手段的探讨[J].中华妇产科杂志,2015,50(4):246-252.
15张宗峰,杜娟.人乳头瘤病毒与微小RNA表达的相关性[J].肿瘤防治研究,2015,42(11):1152-1155.
16梁洁琼,赵敏.高危型人乳头瘤病毒整合态与宫颈上皮内瘤变及宫颈癌关系的探讨[J].中国药物与临床,2014,14(4):431-433.
17 Kang L,Zhao F,Chen F,et al.Value of high risk human papillomavirus viral load in predicting cervical lesions and triaging for high risk(HR)-HPV-positive women[J].Zhonghua Zhong Liu Za Zhi,2014,36(4):316-320.
18 Koukos G,Polytarchou C,Kaplan JL,et al.Micro RNA-124regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis[J].Gastroenterology,2013,145(4):842-852.
19苗小艳,孔繁斗,石敏,等.HPV16/18感染导致宫颈癌的分子机制研究[J].中国微生态学杂志,2015,27(10):1152-1155.
20辛婧,徐银胜,张芳,等.Micro RNA-124对人宫颈癌的抑制作用及机制研究[J].中国生物工程杂志,2015,35(10):13-19.