CDK8和β-catenin在宫颈鳞状细胞癌中的表达及临床意义

发布时间：2018-03-06 03:08

本文选题：CDK8　切入点：β-catenin　出处：《吉林大学》2014年硕士论文　论文类型：学位论文

【摘要】：背景宫颈癌（cervicalcancer）是起源于宫颈上皮的恶性肿瘤，是我国发病率和病死率最高的女性生殖道恶性肿瘤。人类乳头瘤病毒(humanpapillomavirus，HPV)感染在宫颈癌的发生中起重要作用，但并非独立因素。宫颈癌的发生、发展是多因素参与的复杂过程，涉及原癌基因的激活、抑癌基因的失活、DNA转录失控等异常，最终导致细胞周期紊乱。周期素依赖性激酶家族（cycline2dependentkinases，CDKs），是调节细胞周期的核心元件，参与人类恶性肿瘤的发生。CDK8是CDKs家族的成员之一，CDK8的高表达与结肠癌、胃癌、黑色素瘤的发生密切相关。但就CDK8在宫颈癌中的表达情况目前研究较少。β-链蛋白（β-catenin）最早作为一种粘附因子被发现，介导上皮细胞间粘附。β-catenin在基因转录中发挥促癌因子的作用，参与了多种恶性肿瘤的发生。目前在结肠癌、肝癌、大肠癌、卵巢癌、宫颈癌中均已发现β-catenin的异常表达，，并认为β-catenin参与了上述肿瘤的发生及演进。目的检测CDK8、β-catenin在宫颈鳞状细胞癌及其癌前病变中的表达，探讨两者在宫颈癌中的关系及临床意义。方法采用非生物素免疫组化检测系统（NoBiotinPolymer-HRP）Powervision二步法检测20例慢性宫颈炎、64例宫颈上皮内瘤变、50例宫颈鳞状细胞癌组织标本中CDK8、β-catenin蛋白的表达情况。结果 1、CDK8在慢性宫颈炎细胞中呈阴性表达，在CIN、宫颈癌中出现CDK8的阳性表达。CDK8在CINI、CINII、CINIII中的表达率分别为45.8%、55%、90%。CINIII、CINII中CDK8的表达率明显高于CIN（IP＜0.05）。CINII与CINIII组织的表达阳性率差异无显著性(P0.05)。CDK8在慢性宫颈炎组、CIN组、宫颈癌组中的阳性表达率分别为：0%、62.5%、86%，呈递增趋势，三组比较差异有显著性（P＜0.001）。 2、β-catenin在慢性宫颈炎细胞中呈细胞膜连续表达，在CIN和宫颈癌中出现细胞质、细胞核染色。β-catenin在CINI、CINII、CINIII中的异常表达率分别为16.7%、45%、65%。CINIII、CINII中β-catenin的异常表达率明显高于CINI（P＜0.05）。β-catenin在慢性宫颈炎组、CIN组、宫颈癌组中异常表达率分别为：0%、40.6%、70%，呈递增趋势，三组比较差异有显著性（P＜0.05）。 3、CDK8在有淋巴结转移的宫颈癌组中的表达率明显高于无淋巴结转移组（P＜0.05），与临床分期、组织分化无关（P＞0.05）。 4、β-catenin在宫颈癌低分化组中的异常表达率高于高、中分化组，有淋巴结转移组的表达率高于无淋巴结转移组，差异有统计学意义（P＜0.05）。β-catenin在宫颈癌中的表达与临床分期无关（P＞0.05）。 5、CDK8和β-catenin在宫颈癌组织中表达呈正相关（r=0.365）。结论： 1、从慢性宫颈炎到宫颈上皮内瘤变到宫颈鳞状细胞癌，CDK8的阳性表达率和β-catenin的异常表达率逐渐增高，说明CDK8和β-catenin可能促进了宫颈癌的发生。 2、CDK8在宫颈鳞状细胞癌中的表达与淋巴结转移情况有关，β-catenin的异常表达与病理分级及淋巴结转移有关，提示CDK8和β-catenin在宫颈癌浸润和转移中发挥一定作用，二者的异常表达可能提示不良预后。 3、CDK8和β-catenin在宫颈鳞状细胞癌中的表达存在正相关，提示二者共同作用于宫颈癌的病变过程。
[Abstract]:background
Cervical cancer (cervicalcancer) is the origin of cervical epithelial malignant tumors, is China's highest incidence and mortality of malignant tumor of the female genital tract. Human papilloma virus (humanpapillomavirus, HPV) infection plays an important role in the occurrence of cervical cancer, but is not an independent factor. The occurrence of cervical cancer development is a complex process many factors involved, involving the activation of oncogenes, inactivation of tumor suppressor genes, DNA transcription control and other abnormalities, eventually leading to cell cycle disorder. Cyclin dependent kinases (cycline2dependentkinases, CDKs), is the core component of cell cycle regulation, the occurrence of.CDK8 in human malignant tumor is a member of CDKs family, and the high expression of CDK8 in gastric cancer, colon cancer, melanoma is closely related to the occurrence of. But the expression of CDK8 in cervical cancer. There is less research on beta chain protein (beta -catenin) as one of the earliest The adhesion factor was found in epithelial cell adhesion mediated by beta. -catenin play a role in promoting cancer gene transcription factor, is involved in a variety of malignant tumors. In colon cancer, liver cancer, colorectal cancer, ovarian cancer, cervical cancer have been found in the abnormal expression of beta -catenin, and that the occurrence and evolution of beta -catenin is involved in the tumor.
objective
To detect the expression of CDK8 and beta -catenin in squamous cell carcinoma of the cervix and its precancerous lesions, and to explore the relationship and clinical significance of the two in cervical cancer.
Method
The expression of CDK8 and beta -catenin protein in 20 cases of chronic cervicitis, 64 cases of cervical intraepithelial neoplasia and 50 cases of cervical squamous cell carcinoma were detected by Powervision two step method with abiotic immuno histochemical detection system (NoBiotinPolymer-HRP).
Result
1, the expression of CDK8 was negative in chronic cervicitis, cells in CIN, the positive expression of CDK8.CDK8 in CINI, CINII in cervical carcinoma, CINIII expression rates were 45.8%, 55%, 90%.CINIII, CINII expression in CDK8 was significantly higher than that of CIN (IP < 0.05) positive expression rate difference between.CINII and CINIII no significant (P0.05).CDK8 in chronic cervicitis group, CIN group, the positive expression rate in cervical cancer group were 0%, 62.5%, 86%, showed an increasing trend, there were significant differences between three groups (P < 0.001).
2, beta -catenin was expressed in the cell membrane for chronic cervicitis, appear in the cytoplasm, CIN and cervical cancer. Beta -catenin nuclear staining in CINI, CINII, CINIII abnormal expression rates were 16.7%, 45%, 65%.CINIII, P -catenin in CINII abnormal expression rate is significantly higher than CINI (P < 0.05). Beta -catenin in chronic cervicitis group, CIN group and cervical cancer group abnormal expression rate were 0%, 40.6%, 70%, showed an increasing trend, there were significant differences between three groups (P < 0.05).
3, the expression rate of CDK8 in the cervical cancer group with lymph node metastasis was significantly higher than that in the non lymph node metastasis group (P < 0.05). It was not related to the clinical stage, and the tissue differentiation was not related (P > 0.05).
The abnormal expression rate of 4, beta -catenin in the poorly differentiated cervical cancer group was higher than that in the high and moderate differentiation group, and the expression rate in the lymph node metastasis group was higher than that in the non lymph node metastasis group. The difference was statistically significant (P < 0.05). The expression of beta -catenin in cervical cancer was not related to the clinical stage (P > 0.05).
5, the expression of CDK8 and beta -catenin in cervical cancer was positively correlated (r=0.365).
Conclusion:
1, from chronic cervicitis to cervical intraepithelial neoplasia to cervical squamous cell carcinoma, the positive expression rate of CDK8 and the abnormal expression rate of -catenin increased gradually, indicating that CDK8 and beta -catenin may promote the occurrence of cervical cancer.
2, the expression of CDK8 and lymph nodes in cervical squamous cell carcinoma metastasis. The abnormal expression and pathological grade and lymph node metastasis of beta -catenin, suggesting that CDK8 and beta -catenin in cervical cancer invasion and metastasis play a certain role, the abnormal expression of two may indicate bad prognosis.
3, there is a positive correlation between the expression of CDK8 and beta -catenin in the squamous cell carcinoma of the cervix, which suggests that the two groups have a common role in the process of cervical cancer.

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.33

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