宫颈病变组织中CDC7和PHH3蛋白的表达及临床意义
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摘要
目的检测不同程度宫颈病变组织中细胞分裂周期蛋白7(CDC7)和磷酸化组蛋白H3(PHH3)的阳性表达水平,探讨其与宫颈癌发生发展的关系。方法回顾性分析144例宫颈疾病患者的组织标本,采用免疫组织化学染色法检测不同宫颈病变组织中CDC7和PHH3蛋白的表达情况,并根据病理学检测结果分析CDC7和PHH3蛋白的阳性表达与宫颈癌临床特征的关系。结果病理学检测结果显示,CDC7和PHH3蛋白在正常宫颈组织、宫颈上皮内瘤变(CIN)Ⅰ级、CINⅡ～Ⅲ级、宫颈腺癌和宫颈鳞癌中的阳性表达率逐渐升高(P﹤0.01)。宫颈脱落细胞学检查结果显示,CDC7和PHH3蛋白在正常宫颈组织、无明确意义的不典型鳞状上皮细胞(ASCUS)、低度鳞状上皮内病变(LSIL)、不除外高度鳞状上皮内病变的不典型鳞状上皮细胞(ASC-H)和高度鳞状上皮内病变(HSIL)中的阳性表达率逐渐升高(P﹤0.01)。Spearmen相关分析结果显示,CDC7阳性表达与PHH3阳性表达呈正相关。结论 CDC7和PHH3蛋白的高表达与宫颈癌的发生、发展、侵袭和转移有关,有望成为评估、预测宫颈癌侵袭转移的指标。
Objective To discuss the positive expression of cell division cycle protein 7(CDC7) and phospho histone H3(PHH3) in different cervical lesions and to explore the clinical significance of CDC7 and PHH3 in the occurrence and development of cervical cancer.Method A retrospective analysis was conducted to investigate the tissue samples from144 patients of cervical lesions,immunohistochemical assay and cervical cytology were performed to detect the positive expression of CDC7 and PHH3 proteins in different cervical lesions,which were discussed based on pathological findings to assess the relationship between the expression of CDC7 and PHH3 and the clinical manifestations of cervical cancer.Result In pathological examinations,the positive expression rates of CDC7 and PHH3 became higher gradually as observed in normal cervical tissues,cervical intraepithelial neoplasia(CIN) I,CIN II-III,cervical adenocarcinoma and cervical squamous cell carcinoma(P<0.01).In cervical cytology,increasing trend of positive expression of CDC7 and PHH3 proteins were noted in normal cervical tissues,atypical squamous cells of undetermined significance(ASCUS),low-grade squamous intraepithelial lesion(LSIL),atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion(ASC-H) and high-grade squamous intraepithelial lesion(HSIL)(P<0.01).Spearman correlation analysis showed that,CDC7 positive expression was positively correlated with PHH3 positive expression.Conclusion The high expression of CDC7 and PHH3 may be related to the occurrence,development,invasion and metastasis of cervical cancer,thus they may become essential indicators for evaluating and predicting the invasion and metastasis of cervical cancer.
Objective To discuss the positive expression of cell division cycle protein 7(CDC7) and phospho histone H3(PHH3) in different cervical lesions and to explore the clinical significance of CDC7 and PHH3 in the occurrence and development of cervical cancer.Method A retrospective analysis was conducted to investigate the tissue samples from144 patients of cervical lesions,immunohistochemical assay and cervical cytology were performed to detect the positive expression of CDC7 and PHH3 proteins in different cervical lesions,which were discussed based on pathological findings to assess the relationship between the expression of CDC7 and PHH3 and the clinical manifestations of cervical cancer.Result In pathological examinations,the positive expression rates of CDC7 and PHH3 became higher gradually as observed in normal cervical tissues,cervical intraepithelial neoplasia(CIN) I,CIN II-III,cervical adenocarcinoma and cervical squamous cell carcinoma(P<0.01).In cervical cytology,increasing trend of positive expression of CDC7 and PHH3 proteins were noted in normal cervical tissues,atypical squamous cells of undetermined significance(ASCUS),low-grade squamous intraepithelial lesion(LSIL),atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion(ASC-H) and high-grade squamous intraepithelial lesion(HSIL)(P<0.01).Spearman correlation analysis showed that,CDC7 positive expression was positively correlated with PHH3 positive expression.Conclusion The high expression of CDC7 and PHH3 may be related to the occurrence,development,invasion and metastasis of cervical cancer,thus they may become essential indicators for evaluating and predicting the invasion and metastasis of cervical cancer.
引文
[1] Xu HH, Zheng LZ, Lin AF, et al. Human papillomavirus(HPV)18 genetic variants and cervical cancer risk in Taizhou area, China[J]. Gene, 2018, 647:192-197.
[2] Rodriguez-Acebes S, Proctor I, Loddo M, et al. Targeting DNA replication before it starts:Cdc7 as a therapeutic target in p53-mutant breast cancers[J]. Am J Pathol, 2010, 177(4):2034-2045.
[3] Wiman KG, Zhivotovsky B. Understanding cell cycle and cell death regulation provides novel weapons against human diseases[J]. J Intern Med, 2017, 281(5):483-495.
[4]侯芸,王华庆,傅凯,等.细胞分裂周期相关蛋白激酶7和微小染色体维持蛋白2的表达与弥漫大B细胞淋巴瘤患者预后的关系[J].中华肿瘤杂志, 2011, 33(12):911-915.
[5] Rodriguez-Acebes S, Proctor I, Loddo M, et al. Targeting DNA replication before it starts:Cdc7 as a therapeutic target in p53-mutant breast cancers[J]. Am J Pathol, 2010, 177(4):2034-2045.
[6] Hess GF, Drong RF, Weiland KL, et al. A human homolog of the yeast CDC7 gene is overexpressed in some tumors and transformed cell lines[J]. Gene, 1998, 211(1):133-140.
[7] Brunner A, Riss P, Heinze G, et al. pHH3 and survivin are co-expressed in high-risk endometrial cancer and are prognostic relevant[J]. Br J Cancer, 2012, 107(1):84-90.
[8] Sillem M, Timme S, Bronsert P, et al. Anti-phosphohistone H3-positive mitoses are linked to pathological response in neoadjuvantly treated breast cancer[J]. Breast Care(Basel),2017, 12(4):244-250.
[9] Montagnoli A, Moll J, Colotta F. Targeting cell division cycle 7 kinase:a new approach for cancer therapy[J]. Clin Cancer Res, 2010, 16(18):4503-4508.
[10] Knockleby J, Kim BJ, Mehta A, et al. Cdk1-mediated phosphorylation of Cdc7 suppresses DNA re-replication[J]. Cell Cycle, 2016, 15(11):1494-1505.
[11]徐瑞云,严晓丽,廉蕊,等. RT-PCR检测子宫内膜腺癌中CDC7和MCM4的表达[J].中国妇幼保健, 2015, 30(35):6360-6362.
[2] Rodriguez-Acebes S, Proctor I, Loddo M, et al. Targeting DNA replication before it starts:Cdc7 as a therapeutic target in p53-mutant breast cancers[J]. Am J Pathol, 2010, 177(4):2034-2045.
[3] Wiman KG, Zhivotovsky B. Understanding cell cycle and cell death regulation provides novel weapons against human diseases[J]. J Intern Med, 2017, 281(5):483-495.
[4]侯芸,王华庆,傅凯,等.细胞分裂周期相关蛋白激酶7和微小染色体维持蛋白2的表达与弥漫大B细胞淋巴瘤患者预后的关系[J].中华肿瘤杂志, 2011, 33(12):911-915.
[5] Rodriguez-Acebes S, Proctor I, Loddo M, et al. Targeting DNA replication before it starts:Cdc7 as a therapeutic target in p53-mutant breast cancers[J]. Am J Pathol, 2010, 177(4):2034-2045.
[6] Hess GF, Drong RF, Weiland KL, et al. A human homolog of the yeast CDC7 gene is overexpressed in some tumors and transformed cell lines[J]. Gene, 1998, 211(1):133-140.
[7] Brunner A, Riss P, Heinze G, et al. pHH3 and survivin are co-expressed in high-risk endometrial cancer and are prognostic relevant[J]. Br J Cancer, 2012, 107(1):84-90.
[8] Sillem M, Timme S, Bronsert P, et al. Anti-phosphohistone H3-positive mitoses are linked to pathological response in neoadjuvantly treated breast cancer[J]. Breast Care(Basel),2017, 12(4):244-250.
[9] Montagnoli A, Moll J, Colotta F. Targeting cell division cycle 7 kinase:a new approach for cancer therapy[J]. Clin Cancer Res, 2010, 16(18):4503-4508.
[10] Knockleby J, Kim BJ, Mehta A, et al. Cdk1-mediated phosphorylation of Cdc7 suppresses DNA re-replication[J]. Cell Cycle, 2016, 15(11):1494-1505.
[11]徐瑞云,严晓丽,廉蕊,等. RT-PCR检测子宫内膜腺癌中CDC7和MCM4的表达[J].中国妇幼保健, 2015, 30(35):6360-6362.