本文選題：CDK8　切入點(diǎn)：β-catenin　出處：《吉林大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：背景 宮頸癌（cervicalcancer）是起源于宮頸上皮的惡性腫瘤，是我國發(fā)病率和病死率最高的女性生殖道惡性腫瘤。人類乳頭瘤病毒(humanpapillomavirus，HPV)感染在宮頸癌的發(fā)生中起重要作用，但并非獨(dú)立因素。宮頸癌的發(fā)生、發(fā)展是多因素參與的復(fù)雜過程，涉及原癌基因的激活、抑癌基因的失活、DNA轉(zhuǎn)錄失控等異常，最終導(dǎo)致細(xì)胞周期紊亂。周期素依賴性激酶家族（cycline2dependentkinases，CDKs），是調(diào)節(jié)細(xì)胞周期的核心元件，參與人類惡性腫瘤的發(fā)生。CDK8是CDKs家族的成員之一，CDK8的高表達(dá)與結(jié)腸癌、胃癌、黑色素瘤的發(fā)生密切相關(guān)。但就CDK8在宮頸癌中的表達(dá)情況目前研究較少。β-鏈蛋白（β-catenin）最早作為一種粘附因子被發(fā)現(xiàn)，介導(dǎo)上皮細(xì)胞間粘附。β-catenin在基因轉(zhuǎn)錄中發(fā)揮促癌因子的作用，參與了多種惡性腫瘤的發(fā)生。目前在結(jié)腸癌、肝癌、大腸癌、卵巢癌、宮頸癌中均已發(fā)現(xiàn)β-catenin的異常表達(dá)，，并認(rèn)為β-catenin參與了上述腫瘤的發(fā)生及演進(jìn)。 目的 檢測CDK8、β-catenin在宮頸鱗狀細(xì)胞癌及其癌前病變中的表達(dá)，探討兩者在宮頸癌中的關(guān)系及臨床意義。 方法 采用非生物素免疫組化檢測系統(tǒng)（NoBiotinPolymer-HRP）Powervision二步法檢測20例慢性宮頸炎、64例宮頸上皮內(nèi)瘤變、50例宮頸鱗狀細(xì)胞癌組織標(biāo)本中CDK8、β-catenin蛋白的表達(dá)情況。 結(jié)果 1、CDK8在慢性宮頸炎細(xì)胞中呈陰性表達(dá)，在CIN、宮頸癌中出現(xiàn)CDK8的陽性表達(dá)。CDK8在CINI、CINII、CINIII中的表達(dá)率分別為45.8%、55%、90%。CINIII、CINII中CDK8的表達(dá)率明顯高于CIN（IP＜0.05）。CINII與CINIII組織的表達(dá)陽性率差異無顯著性(P0.05)。CDK8在慢性宮頸炎組、CIN組、宮頸癌組中的陽性表達(dá)率分別為：0%、62.5%、86%，呈遞增趨勢，三組比較差異有顯著性（P＜0.001）。 2、β-catenin在慢性宮頸炎細(xì)胞中呈細(xì)胞膜連續(xù)表達(dá)，在CIN和宮頸癌中出現(xiàn)細(xì)胞質(zhì)、細(xì)胞核染色。β-catenin在CINI、CINII、CINIII中的異常表達(dá)率分別為16.7%、45%、65%。CINIII、CINII中β-catenin的異常表達(dá)率明顯高于CINI（P＜0.05）。β-catenin在慢性宮頸炎組、CIN組、宮頸癌組中異常表達(dá)率分別為：0%、40.6%、70%，呈遞增趨勢，三組比較差異有顯著性（P＜0.05）。 3、CDK8在有淋巴結(jié)轉(zhuǎn)移的宮頸癌組中的表達(dá)率明顯高于無淋巴結(jié)轉(zhuǎn)移組（P＜0.05），與臨床分期、組織分化無關(guān)（P＞0.05）。 4、β-catenin在宮頸癌低分化組中的異常表達(dá)率高于高、中分化組，有淋巴結(jié)轉(zhuǎn)移組的表達(dá)率高于無淋巴結(jié)轉(zhuǎn)移組，差異有統(tǒng)計學(xué)意義（P＜0.05）。β-catenin在宮頸癌中的表達(dá)與臨床分期無關(guān)（P＞0.05）。 5、CDK8和β-catenin在宮頸癌組織中表達(dá)呈正相關(guān)（r=0.365）。 結(jié)論： 1、從慢性宮頸炎到宮頸上皮內(nèi)瘤變到宮頸鱗狀細(xì)胞癌，CDK8的陽性表達(dá)率和β-catenin的異常表達(dá)率逐漸增高，說明CDK8和β-catenin可能促進(jìn)了宮頸癌的發(fā)生。 2、CDK8在宮頸鱗狀細(xì)胞癌中的表達(dá)與淋巴結(jié)轉(zhuǎn)移情況有關(guān)，β-catenin的異常表達(dá)與病理分級及淋巴結(jié)轉(zhuǎn)移有關(guān)，提示CDK8和β-catenin在宮頸癌浸潤和轉(zhuǎn)移中發(fā)揮一定作用，二者的異常表達(dá)可能提示不良預(yù)后。 3、CDK8和β-catenin在宮頸鱗狀細(xì)胞癌中的表達(dá)存在正相關(guān)，提示二者共同作用于宮頸癌的病變過程。
[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.

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.33

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