miR-143在宫颈鳞癌组织中的表达及意义
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摘要
背景与目的
宫颈癌是全球女性最常见的恶性肿瘤之一,尤其在发展中国家,造成每年约35万人死亡,且近来有年轻化趋势,严重威胁女性的生育及健康,构成了一个重要的公共健康问题,是我国重点防治癌症之一。大约80%的原发性宫颈癌从鳞状上皮不典型增生发生。高危型人乳头状瘤病毒(HPV)感染为宫颈癌发生的主要原因。然而,HPV阴性者也可患宫颈癌。这表明,其他辅助因子中存在从宫颈不典型增生到宫颈癌之间的致病因素。microRNA的发现,为癌症的发病机理提供了新的思路,它在转录后水平上调控基因表达。深入研究宫颈癌发生及发展的分子机制,寻找具有早期诊断的分子标志物,发现有效的治疗靶点,对于提高宫颈癌的诊断和治疗具有重要的意义。
miRNAs是一类长度约19-25nt的单链非编码RNA,负调控靶mRNAs翻译的稳定性和效率。可在疾病中观察到miRNAs表达的变化,特别是在癌症中。miRNA的监管失调可能在宫颈癌的发生和发展过程中起重要作用。miR-143位于染色体5q32处。在多种恶性肿瘤中均呈低表达。miR-143在宫颈癌肿瘤诊断和治疗中可能存在潜在的应用价值。虽然miR-143在宫颈癌细胞株中呈现低表达,但目前国内尚未发现miR-143在正常宫颈组织、宫颈上皮内瘤变组织(CIN)及宫颈鳞癌组织中的研究。本研究旨在研究在正常宫颈组织、宫颈上皮内瘤变组织(CIN)及宫颈鳞癌组织中miR-143表达水平的变化,为miR-143在宫颈鳞癌中的研究提供理论基础。
材料与方法
1实验分组
1.1病例组：选取郑州大学第二附属医院2012年2月至2012年11月住院手术切除的30例新鲜宫颈鳞状细胞癌组织,按国际妇产科联盟(FIGO)的分期标准,Ⅰ期20例,Ⅱ期10例。30例门诊收集的新鲜宫颈上皮内瘤变组织(CIN),其中CIN级14例,CIN～Ⅲ级16例。
1.2对照组：取同期因子宫肌瘤行全子宫切除的正常宫颈组织30例作为对照。
1.3纳入标准：①所有病例均未行放疗和化疗：②所有病理组织均经病理检查为宫颈鳞癌或宫颈上皮内瘤变;③所有入选的标本征集均经患者或家属的同意,并签知情同意书。
2.实验方法
用实时荧光定量聚合酶链反应(qRT-PCR)方法检测正常宫颈组织、CIN和宫颈鳞癌组织中miR-143的表达水平。用U6作为内参。应用统计软件SPSS17.0进行数据分析,计量资料以均数±标准差(x±s)表示,组间均数比较采用独立样本T检验,多个样本均数比较采用单因素方差分析。检验水准a=0.05。P<0.05差异有统计学意义。
结果
1.在正常宫颈组织、CIN组织和宫颈鳞癌组织中miR-143的相对表达量分别为1.02±0.15、0.93±0.17、0.32±0.23,三者比较差别具有统计学意义(F=122.097,P<0.05)。用LSD统计方法对其进行两两比较,发现正常宫颈组织和CIN组织比较差别无统计学意义(P>0.05),正常宫颈组织和CIN组织与宫颈鳞状细胞癌组织比较差别均有统计学意义(P<0.05)。
2.miR-143在高危型HPV阳性和阴性中的相对表达量分别为0.87±0.27、0.90±0.24,两组比较差别无统计学意义(t=0.453,P>0.05)。
3.宫颈鳞癌组织病理分级G2期与G3期miR-143的相对表达量为0.38±0.47、0.15±0.33,两者比较差别有统计学意义(t=2.742,P<0.05)。
4.宫颈鳞癌淋巴结阳性和阴性miR-143的表达量为0.17±0.40、0.37±0.47,两者比较差异具有统计学意义(t=2.506,P<0.05)。
5.宫颈鳞癌肿瘤直径≥2.5cm和肿瘤直径<2.5cm miR-143的相对表达量为0.22±0.06、0.36±0.48,两者比较差别无统计学意义(t=1.709,P>0.05)。
6.宫颈鳞癌间质浸润深度≥2/5和间质浸润深度<2/5miR-143的相对表达量为0.31±0.44、0.33±0.89,两者比较差别无统计学意义(t=-0.269,P>0.05)。
7.宫颈鳞癌FIGOI期和II期miR-143的相对表达量为0.36±0.54、0.24±0.41,两者比较差别无统计学意义(t=1.455,P>0.05)。
8.宫颈鳞癌年龄>40岁和年龄<40岁miR-143的相对表达量为0.31+0.52、0.33±0.57,两者比较差异无统计学意义(t=0.249,P>0.05)。
结论
1.miR-143的低表达水平与宫颈鳞癌相关；
2.miR-143的表达水平与高危型HPV感染无关；
3.宫颈鳞癌中miR-143的表达水平与组织病理分级和淋巴结转移相关,与肿瘤直径、间质浸润深度、临床分期和年龄无关。
Background and objective
Cervical cancer is one of the most common cancers in women worldwide, especially in developing countries,which caused about35million deaths per year. The people who have it get younger and younger. Cervical cancer which is one of important cancer prevention in China had threatened to fertility and health of women,and it poses an important public health problem. Approximately80%of primary cervical cancers arise from pre-existing squamous dysplasia. The most important etiologic agent in the pathogenesis is high risk human papillomavirus (HPV). However, the people who are HPV-negative also got cervical cancer.This suggests that other cofactors must be present in the pathogenic pathway between cervical dysplasia and carcinoma.The discover of microRNA which in the post-transcriptional level regulate the expression of gene provides new ideas for the pathogenesis of cancer.It is very significantly to improve the diagnosis and treatment of cervical cancer in studying the molecular mechanism deeply, seeking molecular markers for early diagnosis and finding effective therapeutic targets.
microRNAs are a class of about19-25nt single-stranded non-coding RNA,which negatively regulate the translational efficiency and stability of target mRNAs. Altered miRNAs expression in disease has been observed, especially in cancer.The deregulation of miRNAs may play an important role in the occurrence and development of cervical cancer. miR-143located in chromosome5q32. miR-143is downregulated in a variety of malignant tumors. miR-143in the diagnosis and treatment of cervical cancer may have potential applications. Although miR-143in cervical cancer cell lines showed low expression, but there is not yet discovered the expression of miR-143in normal cervical tissue, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma. This research aimed to study the expression level of miR-143in normal cervical tissue, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma,and provide a theoretical basis for study of miR-143in cervical squamous cell carcinoma.
Materials and Methods
1. The experimental group
1.1The case group:According to the International Federation of Gynecology and Obstetrics (FIGO) staging system,30samples of fresh cervical squamous cell carcinoma tissues come from the Second Affiliated Hospital of Zhengzhou University between February2012and November2012, which consist of Ⅰ20samples, Ⅱ10samples.30samples of fresh cervical intraepithelial neoplasia (CIN) tissues were collected in the same time, which consist of CIN Ⅰ14samples, CIN Ⅱ-Ⅲ16samples.
1.2The control group:30samples of normal cervical tissues due to uterine fibroids hysterectomy were collected in the same period as a control.
1.3The inclusion criteria:①All the samples have not been treated by radiotherapy and chemotherapy;②All cervical tissues were examined by pathological diagnosis as cervical squamous cell carcinoma or cervical intraepithelial neoplasia tissues;③The patients or thire family all agreed with the samples selection and signed informed consent.
2. The experiment method
Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) method was used to detect the relative expression of miR-143in the tissues of normal cervical, CIN and cervical squamous cell carcinoma.With U6as an internal reference. The date were analyzed by SPSS17.0program. The measurement data were expressed as standard deviation(x±s) and tested by independent samples T-test or One-Way ANOVA.Inspection level is α=0.05. P<0.05is the level of significant difference.
Results
1.The average relative expression of miR-143in normal cervical tissues, CIN tissues and cervical squamous cell carcinoma tissues were1.02±0.15、0.93±0.17、0.32±0.23, the difference was statistically significant (F=122.097, P<0.05).Comparing the pairwise comparisons with LSD statistical methods,between normal cervical tissues and CIN tissues the difference was not statistically significant (P>0.05),between cervical squamous cell carcinoma tissues and normal cervical tissues and CIN tissues the difference was statistically significant (P<0.05).
2.The average relative expression of miR-143in the high-risk HPV positive and negative were0.87±0.27,0.90±0.24,the comparion between the two groups was not statistically significant difference(t=0.453,P>0.05).
3.The average relative expression of miR-143in Cervical squamous cell carcinoma pathological stage G2and G3were0.38±0.47and0.15±0.33, the comparion between the two groups was not statistically significant difference (t=2.742,P<0.05)
4.The average relative expression of miR-143in cervical squamous cell carcinoma with positive and negative lymph nodes were0.17±0.40and0.37±0.47, the comparion between the two groups was not statistically significant difference (t=2.506, P<0.05).
5.The average relative expression of miR-143in cervical squamous cell carcinoma with tumor diameter≥2.5cm and<2.5cm were0.22±0.06,0.36±0.48, the comparion between the two groups was not statistically significant difference (t=1.709, P>0.05).
6.The average relative expression of miR-143in cervical squamous cell with interstitial infiltration depth≥2/5and <2/5were0.31±0.44,0.33±0.89, the comparion between the two groups was not statistically significant difference (t=-0.269,P>0.05).
7.The average relative expression of miR-143in cervical squamous cell carcinoma FIGO Ⅰ and Ⅱ were0.36±0.54,0.24±0.41, the comparion between the two groups was not statistically significant difference (t=1.455, P>0.05).
8.The average relative expression of miR-143in cervical squamous cell carcinoma with the young(≥40)and the old (<40) were0.31±0.52,0.33±0.57, the comparion between the two groups was not statistically significant difference (t=0.249, P>0.05).
Conclusions:
l.The low expression level of miR-143are significantly associated with cervical squamous cell carcinoma.
2.The expression level of miR-143are not significantly associated with high risk HPV infection.
3.The expression level of miR-143in cervical squamous cell carcinoma are significantly associated with pathological stage, lymph node metastasis;but not associated with tumor size, depth of stromal invasion, clinical stage, and age.
宫颈癌是全球女性最常见的恶性肿瘤之一,尤其在发展中国家,造成每年约35万人死亡,且近来有年轻化趋势,严重威胁女性的生育及健康,构成了一个重要的公共健康问题,是我国重点防治癌症之一。大约80%的原发性宫颈癌从鳞状上皮不典型增生发生。高危型人乳头状瘤病毒(HPV)感染为宫颈癌发生的主要原因。然而,HPV阴性者也可患宫颈癌。这表明,其他辅助因子中存在从宫颈不典型增生到宫颈癌之间的致病因素。microRNA的发现,为癌症的发病机理提供了新的思路,它在转录后水平上调控基因表达。深入研究宫颈癌发生及发展的分子机制,寻找具有早期诊断的分子标志物,发现有效的治疗靶点,对于提高宫颈癌的诊断和治疗具有重要的意义。
miRNAs是一类长度约19-25nt的单链非编码RNA,负调控靶mRNAs翻译的稳定性和效率。可在疾病中观察到miRNAs表达的变化,特别是在癌症中。miRNA的监管失调可能在宫颈癌的发生和发展过程中起重要作用。miR-143位于染色体5q32处。在多种恶性肿瘤中均呈低表达。miR-143在宫颈癌肿瘤诊断和治疗中可能存在潜在的应用价值。虽然miR-143在宫颈癌细胞株中呈现低表达,但目前国内尚未发现miR-143在正常宫颈组织、宫颈上皮内瘤变组织(CIN)及宫颈鳞癌组织中的研究。本研究旨在研究在正常宫颈组织、宫颈上皮内瘤变组织(CIN)及宫颈鳞癌组织中miR-143表达水平的变化,为miR-143在宫颈鳞癌中的研究提供理论基础。
材料与方法
1实验分组
1.1病例组：选取郑州大学第二附属医院2012年2月至2012年11月住院手术切除的30例新鲜宫颈鳞状细胞癌组织,按国际妇产科联盟(FIGO)的分期标准,Ⅰ期20例,Ⅱ期10例。30例门诊收集的新鲜宫颈上皮内瘤变组织(CIN),其中CIN级14例,CIN～Ⅲ级16例。
1.2对照组：取同期因子宫肌瘤行全子宫切除的正常宫颈组织30例作为对照。
1.3纳入标准：①所有病例均未行放疗和化疗：②所有病理组织均经病理检查为宫颈鳞癌或宫颈上皮内瘤变;③所有入选的标本征集均经患者或家属的同意,并签知情同意书。
2.实验方法
用实时荧光定量聚合酶链反应(qRT-PCR)方法检测正常宫颈组织、CIN和宫颈鳞癌组织中miR-143的表达水平。用U6作为内参。应用统计软件SPSS17.0进行数据分析,计量资料以均数±标准差(x±s)表示,组间均数比较采用独立样本T检验,多个样本均数比较采用单因素方差分析。检验水准a=0.05。P<0.05差异有统计学意义。
结果
1.在正常宫颈组织、CIN组织和宫颈鳞癌组织中miR-143的相对表达量分别为1.02±0.15、0.93±0.17、0.32±0.23,三者比较差别具有统计学意义(F=122.097,P<0.05)。用LSD统计方法对其进行两两比较,发现正常宫颈组织和CIN组织比较差别无统计学意义(P>0.05),正常宫颈组织和CIN组织与宫颈鳞状细胞癌组织比较差别均有统计学意义(P<0.05)。
2.miR-143在高危型HPV阳性和阴性中的相对表达量分别为0.87±0.27、0.90±0.24,两组比较差别无统计学意义(t=0.453,P>0.05)。
3.宫颈鳞癌组织病理分级G2期与G3期miR-143的相对表达量为0.38±0.47、0.15±0.33,两者比较差别有统计学意义(t=2.742,P<0.05)。
4.宫颈鳞癌淋巴结阳性和阴性miR-143的表达量为0.17±0.40、0.37±0.47,两者比较差异具有统计学意义(t=2.506,P<0.05)。
5.宫颈鳞癌肿瘤直径≥2.5cm和肿瘤直径<2.5cm miR-143的相对表达量为0.22±0.06、0.36±0.48,两者比较差别无统计学意义(t=1.709,P>0.05)。
6.宫颈鳞癌间质浸润深度≥2/5和间质浸润深度<2/5miR-143的相对表达量为0.31±0.44、0.33±0.89,两者比较差别无统计学意义(t=-0.269,P>0.05)。
7.宫颈鳞癌FIGOI期和II期miR-143的相对表达量为0.36±0.54、0.24±0.41,两者比较差别无统计学意义(t=1.455,P>0.05)。
8.宫颈鳞癌年龄>40岁和年龄<40岁miR-143的相对表达量为0.31+0.52、0.33±0.57,两者比较差异无统计学意义(t=0.249,P>0.05)。
结论
1.miR-143的低表达水平与宫颈鳞癌相关；
2.miR-143的表达水平与高危型HPV感染无关；
3.宫颈鳞癌中miR-143的表达水平与组织病理分级和淋巴结转移相关,与肿瘤直径、间质浸润深度、临床分期和年龄无关。
Background and objective
Cervical cancer is one of the most common cancers in women worldwide, especially in developing countries,which caused about35million deaths per year. The people who have it get younger and younger. Cervical cancer which is one of important cancer prevention in China had threatened to fertility and health of women,and it poses an important public health problem. Approximately80%of primary cervical cancers arise from pre-existing squamous dysplasia. The most important etiologic agent in the pathogenesis is high risk human papillomavirus (HPV). However, the people who are HPV-negative also got cervical cancer.This suggests that other cofactors must be present in the pathogenic pathway between cervical dysplasia and carcinoma.The discover of microRNA which in the post-transcriptional level regulate the expression of gene provides new ideas for the pathogenesis of cancer.It is very significantly to improve the diagnosis and treatment of cervical cancer in studying the molecular mechanism deeply, seeking molecular markers for early diagnosis and finding effective therapeutic targets.
microRNAs are a class of about19-25nt single-stranded non-coding RNA,which negatively regulate the translational efficiency and stability of target mRNAs. Altered miRNAs expression in disease has been observed, especially in cancer.The deregulation of miRNAs may play an important role in the occurrence and development of cervical cancer. miR-143located in chromosome5q32. miR-143is downregulated in a variety of malignant tumors. miR-143in the diagnosis and treatment of cervical cancer may have potential applications. Although miR-143in cervical cancer cell lines showed low expression, but there is not yet discovered the expression of miR-143in normal cervical tissue, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma. This research aimed to study the expression level of miR-143in normal cervical tissue, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma,and provide a theoretical basis for study of miR-143in cervical squamous cell carcinoma.
Materials and Methods
1. The experimental group
1.1The case group:According to the International Federation of Gynecology and Obstetrics (FIGO) staging system,30samples of fresh cervical squamous cell carcinoma tissues come from the Second Affiliated Hospital of Zhengzhou University between February2012and November2012, which consist of Ⅰ20samples, Ⅱ10samples.30samples of fresh cervical intraepithelial neoplasia (CIN) tissues were collected in the same time, which consist of CIN Ⅰ14samples, CIN Ⅱ-Ⅲ16samples.
1.2The control group:30samples of normal cervical tissues due to uterine fibroids hysterectomy were collected in the same period as a control.
1.3The inclusion criteria:①All the samples have not been treated by radiotherapy and chemotherapy;②All cervical tissues were examined by pathological diagnosis as cervical squamous cell carcinoma or cervical intraepithelial neoplasia tissues;③The patients or thire family all agreed with the samples selection and signed informed consent.
2. The experiment method
Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) method was used to detect the relative expression of miR-143in the tissues of normal cervical, CIN and cervical squamous cell carcinoma.With U6as an internal reference. The date were analyzed by SPSS17.0program. The measurement data were expressed as standard deviation(x±s) and tested by independent samples T-test or One-Way ANOVA.Inspection level is α=0.05. P<0.05is the level of significant difference.
Results
1.The average relative expression of miR-143in normal cervical tissues, CIN tissues and cervical squamous cell carcinoma tissues were1.02±0.15、0.93±0.17、0.32±0.23, the difference was statistically significant (F=122.097, P<0.05).Comparing the pairwise comparisons with LSD statistical methods,between normal cervical tissues and CIN tissues the difference was not statistically significant (P>0.05),between cervical squamous cell carcinoma tissues and normal cervical tissues and CIN tissues the difference was statistically significant (P<0.05).
2.The average relative expression of miR-143in the high-risk HPV positive and negative were0.87±0.27,0.90±0.24,the comparion between the two groups was not statistically significant difference(t=0.453,P>0.05).
3.The average relative expression of miR-143in Cervical squamous cell carcinoma pathological stage G2and G3were0.38±0.47and0.15±0.33, the comparion between the two groups was not statistically significant difference (t=2.742,P<0.05)
4.The average relative expression of miR-143in cervical squamous cell carcinoma with positive and negative lymph nodes were0.17±0.40and0.37±0.47, the comparion between the two groups was not statistically significant difference (t=2.506, P<0.05).
5.The average relative expression of miR-143in cervical squamous cell carcinoma with tumor diameter≥2.5cm and<2.5cm were0.22±0.06,0.36±0.48, the comparion between the two groups was not statistically significant difference (t=1.709, P>0.05).
6.The average relative expression of miR-143in cervical squamous cell with interstitial infiltration depth≥2/5and <2/5were0.31±0.44,0.33±0.89, the comparion between the two groups was not statistically significant difference (t=-0.269,P>0.05).
7.The average relative expression of miR-143in cervical squamous cell carcinoma FIGO Ⅰ and Ⅱ were0.36±0.54,0.24±0.41, the comparion between the two groups was not statistically significant difference (t=1.455, P>0.05).
8.The average relative expression of miR-143in cervical squamous cell carcinoma with the young(≥40)and the old (<40) were0.31±0.52,0.33±0.57, the comparion between the two groups was not statistically significant difference (t=0.249, P>0.05).
Conclusions:
l.The low expression level of miR-143are significantly associated with cervical squamous cell carcinoma.
2.The expression level of miR-143are not significantly associated with high risk HPV infection.
3.The expression level of miR-143in cervical squamous cell carcinoma are significantly associated with pathological stage, lymph node metastasis;but not associated with tumor size, depth of stromal invasion, clinical stage, and age.
引文
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