本文選題：Bmi-1 + OPN��； 參考：《鄭州大學(xué)》2014年碩士論文

【摘要】：背景與目的 宮頸癌是威脅女性健康最常見的第二大惡性腫瘤，且發(fā)病年齡逐漸年輕化，而影響其病死率及預(yù)后的主要因素是宮頸癌的浸潤(rùn)和轉(zhuǎn)移。在宮頸癌的發(fā)展過程中，存在著各種與浸潤(rùn)轉(zhuǎn)移相關(guān)的癌基因的激活和抑癌基因的失活。因此，臨床中對(duì)宮頸癌的治療和預(yù)后判斷有賴于對(duì)宮頸癌的發(fā)生發(fā)展、浸潤(rùn)轉(zhuǎn)移機(jī)制的分子生物學(xué)的研究。近年研究表明，上皮-間質(zhì)轉(zhuǎn)化(epithelial-mesenchymaltransformation，EMT)與上皮細(xì)胞來(lái)源的腫瘤的浸潤(rùn)、轉(zhuǎn)移有關(guān)，在口腔癌、肺癌、乳腺癌、肝癌、結(jié)腸癌、卵巢癌、前列腺癌等許多惡性腫瘤的原位浸潤(rùn)和遠(yuǎn)處轉(zhuǎn)移過程中發(fā)揮了重要作用[1]。E-鈣粘蛋白（E-cadherin）的表達(dá)下調(diào)和波形蛋白（Vimentin）的表達(dá)上調(diào)是EMT發(fā)生的主要特征。原癌基因Bmi-1(B-cell-specific Moloneymurine leukemia virus insertion site l，，BMI-1)是多梳基因(polycomb group genes，PcG)家族中的成員之一，在細(xì)胞的生長(zhǎng)、增殖、凋亡調(diào)節(jié)和干細(xì)胞的自我更新中起著非常重要的作用[2]。研究表明，Bmi-1在許多腫瘤中表達(dá)上調(diào)，與惡性腫瘤的惡性轉(zhuǎn)化有明顯相關(guān)性。骨橋蛋白（osteopontin，OPN）是一種鈣結(jié)合磷酸蛋白。多項(xiàng)研究顯示，骨橋蛋白與腫瘤的浸潤(rùn)、轉(zhuǎn)移和惡性轉(zhuǎn)化有密切相關(guān)性，所以O(shè)PN基因又被稱為腫瘤轉(zhuǎn)移相關(guān)基因。目前，在宮頸癌的浸潤(rùn)轉(zhuǎn)移方面針對(duì)Bmi-1、OPN的研究文獻(xiàn)較少。本課題通過檢測(cè)Bmi-1、OPN和EMT分子標(biāo)記蛋白E-cadherin、Vimentin在宮頸癌變過程中的表達(dá)，并分析其相關(guān)性，探討B(tài)mi-1、OPN在宮頸鱗癌浸潤(rùn)、轉(zhuǎn)移過程中的作用。 材料與方法 1、標(biāo)本來(lái)源：收集2012年6月至2013年7月鄭州大學(xué)第二附屬醫(yī)院病理科存檔的宮頸蠟塊標(biāo)本126例，其中包括因子宮肌瘤行子宮全切術(shù)的正常宮頸組織20例、60例CIN組織（CINⅠ25例、CINⅡ19例和CINⅢ16例）和術(shù)前未經(jīng)放化療且術(shù)后病理確診的宮頸鱗癌組織46例。 2、實(shí)驗(yàn)方法：采用免疫組化SP法檢測(cè)20例正常宮頸組織、60例CIN組織（CINⅠ25例、CINⅡ19例和CINⅢ16例）和46例宮頸鱗癌組織中Bmi-1、OPN、 E-cadherin和Vimentin的表達(dá)，并分析其相關(guān)性。 3、統(tǒng)計(jì)方法：采用SPSS17.0統(tǒng)計(jì)軟件包對(duì)數(shù)據(jù)進(jìn)行分析處理，定性資料的比較采用卡方檢驗(yàn)或Fisher確切概率法，利用2×2配對(duì)資料進(jìn)行相關(guān)分析。以P0.05定義為差別有統(tǒng)計(jì)學(xué)意義。 結(jié)果 1、Bmi-1的表達(dá)：正常宮頸組織、CIN和宮頸鱗狀細(xì)胞癌組織中Bmi-1蛋白主要定位在細(xì)胞核中。Bmi-1在正常宮頸組、CIN組和宮頸鱗癌組中的表達(dá)逐漸升高，總體有差異（P＜0.05）；其中正常宮頸組和宮頸鱗癌組、CIN組和宮頸鱗癌組相比均有差異（P＜0.05）。Bmi-1在CINⅠ、CINⅡ和CINⅢ中的表達(dá)有差異（P＜0.05），其中CINⅠ和CINⅢ相比有差異（P＜0.05）。宮頸鱗癌組織中，Bmi-1蛋白的表達(dá)與患者的臨床分期、組織學(xué)分級(jí)和淋巴結(jié)轉(zhuǎn)移有關(guān)（P＜0.05）。 2、OPN的表達(dá)：正常宮頸組織、CIN和宮頸鱗狀細(xì)胞癌組織中OPN蛋白主要定位在細(xì)胞質(zhì)和細(xì)胞核中。OPN在正常宮頸組、CIN組和宮頸鱗癌組中的表達(dá)逐漸升高，總體有差異（P＜0.05）；其中正常宮頸組和宮頸鱗癌組、CIN組和宮頸鱗癌組比較均有差異（P＜0.05）。OPN在CINⅠ、CINⅡ和CINⅢ中的表達(dá)無(wú)差異（P＜0.05），其中兩兩比較也無(wú)差異（P＞0.05）。宮頸鱗癌組織中，OPN蛋白的表達(dá)與患者的臨床分期、組織學(xué)分級(jí)、組織浸潤(rùn)深度和淋巴結(jié)轉(zhuǎn)移有關(guān)（P＜0.05）。 3、E-cadherin的表達(dá)：在正常宮頸組織、CIN和宮頸鱗癌組織中E-cadherin蛋白主要定位于細(xì)胞膜。E-cadherin在正常宮頸組、CIN組和宮頸鱗癌組中的表達(dá)逐步降低，總體有差異（P＜0.05）；其中兩兩之間相比均有差異（P＜0.05）。E-cadherin在CINⅠ、CINⅡ和CINⅢ中的表達(dá)無(wú)差異（P＜0.05），其中兩兩比較差異也均無(wú)差異（P＞0.05）。宮頸鱗癌組織中，E-cadherin蛋白的表達(dá)與患者的臨床分期、組織學(xué)分級(jí)、組織浸潤(rùn)深度和淋巴結(jié)轉(zhuǎn)移有關(guān)（P＜0.05）。 4、Vimentin的表達(dá)：Vimentin在正常宮頸組織中不表達(dá)，在CIN和宮頸鱗狀細(xì)胞癌組織中Vimentin蛋白主要定位在細(xì)胞質(zhì)中。Vimentin在CIN組和宮頸鱗癌組中的表達(dá)逐步升高，總體有差異（P＜0.05）；其中正常宮頸組和宮頸鱗癌組、CIN組和宮頸鱗癌組相比均有差異（P＜0.05）。Vimentin在CINⅠ、CINⅡ和CINⅢ中的表達(dá)差異無(wú)統(tǒng)計(jì)學(xué)意義（P＜0.05），其中兩兩相比差別也均無(wú)統(tǒng)計(jì)學(xué)意義（P＞0.05）。宮頸鱗癌組織中，Vimentin蛋白的表達(dá)與患者的組織浸潤(rùn)深度、臨床分期和淋巴結(jié)轉(zhuǎn)移有關(guān)（P＜0.05）。 5、宮頸鱗癌組織中Bmi-1、OPN、E-cadherin以及Vimentin的相關(guān)性： ⑴Bmi-1與E-cadherin的表達(dá)是負(fù)相關(guān)（r=-0.531,P＜0.05），與Vimentin的表達(dá)是正相關(guān)（r=0.344,P＜0.05）； ⑵OPN與E-cadherin表達(dá)是負(fù)相關(guān)（r=-0.544,P＜0.05），與Vimentin表達(dá)是正相關(guān)（r=0.368,P＜0.05）； ⑶Bmi-1與OPN表達(dá)是正相關(guān)（r=0.507,P＜0.05）； ⑷E-cadherin與Vimentin表達(dá)是負(fù)相關(guān)（r=-0.341,P＜0.05）。 結(jié)論 1、原癌基因Bmi-1、腫瘤轉(zhuǎn)移相關(guān)基因OPN的高表達(dá)與宮頸鱗癌的組織學(xué)分級(jí)、臨床分期和淋巴結(jié)轉(zhuǎn)移密切相關(guān)，提示Bmi-1、OPN可能在宮頸鱗癌的發(fā)生發(fā)展和浸潤(rùn)轉(zhuǎn)移過程當(dāng)中發(fā)揮了重要作用。 2、Bmi-1、OPN可能是通過上皮-間質(zhì)轉(zhuǎn)化促進(jìn)宮頸鱗癌的浸潤(rùn)和轉(zhuǎn)移。 3、Bmi-1與OPN在宮頸鱗癌中的表達(dá)呈正相關(guān)，提示兩者可能協(xié)同促進(jìn)宮頸癌的浸潤(rùn)和轉(zhuǎn)移。
[Abstract]:Background and purpose
Cervical cancer is the second most common malignant tumor that threatens the health of women, and the age of the disease is gradually younger. The main factor affecting the mortality and prognosis is the invasion and metastasis of cervical cancer. In the development of cervical cancer, there are various activation and inactivation of tumor suppressor genes associated with infiltration and metastasis. The treatment and prognosis of cervical cancer depends on the development of cervical cancer and the molecular biology of the mechanism of invasion and metastasis. Recent studies have shown that epithelial mesenchymal transformation (epithelial-mesenchymaltransformation, EMT) is related to the invasion and metastasis of epithelial cells, and in oral cancer, lung cancer, breast cancer, liver cancer, colon, and colon In situ infiltration and distant metastasis of many malignant tumors such as cancer, ovarian cancer and prostate cancer have played an important role in the downregulation of [1].E- cadherin (E-cadherin) expression and the up-regulation of vimentin (Vimentin) expression is the main feature of EMT. The proto oncogene Bmi-1 (B-cell-specific Moloneymurine leukemia virus insertion site L) BMI-1) is one of the members of the Polycomb group genes (PcG) family, which plays a very important role in cell growth, proliferation, apoptosis regulation and the self-renewal of stem cells. [2]. studies show that Bmi-1 is up regulated in many tumors and has a significant correlation with malignant transformation of malignant tumor. Osteopontin (osteopontin, OPN) It is a calcium binding phosphate protein. A number of studies have shown that osteopontin is closely related to tumor invasion, metastasis and malignant transformation, so the OPN gene is also known as tumor metastasis related genes. At present, there are few studies on Bmi-1 and OPN in the invasion and metastasis of cervical cancer. This topic is based on the detection of Bmi-1, OPN and EMT molecular markers. The expression of protein E-cadherin and Vimentin in cervical carcinogenesis was analyzed, and the correlation between Bmi-1 and OPN in the process of invasion and metastasis of cervical squamous cell carcinoma was discussed.
Materials and methods
1, specimen sources: 126 cases of cervix paraffin specimens collected from the pathology department of the Second Affiliated Hospital of Zhengzhou University from June 2012 to July 2013 were collected, including 20 cases of normal cervical tissue with hysteromyoma undergoing hysterectomy, 60 cases of CIN tissue (CIN I 25 cases, CIN II 19 cases and CIN III 16 cases), and preoperative and postoperative pathologic diagnosis of the uterus. 46 cases of squamous cell carcinoma of the neck.
2, experimental methods: the expression of Bmi-1, OPN, E-cadherin and Vimentin in 20 cases of normal cervical tissue, 60 cases of CIN tissue (CIN I 25 cases, CIN II 19 cases and CIN III 16 cases) and 46 cases of cervical squamous cell carcinoma were detected by immunohistochemical SP method, and the correlation was analyzed.
3, statistical method: the data were analyzed with SPSS17.0 software package. Qualitative data were compared with chi square test or Fisher exact probability method, and 2 x 2 paired data were used for correlation analysis. The difference was statistically significant with the definition of P0.05.
Result
1, Bmi-1 expression: the expression of Bmi-1 protein in normal cervical tissue, CIN and cervical squamous cell carcinoma was mainly located in the nucleus.Bmi-1 in the normal cervix group, the CIN group and the cervical squamous cell carcinoma group gradually increased (P < 0.05), and the normal cervix group and the cervical squamous cell carcinoma group, the CIN group and the cervical squamous cell carcinoma group were different (P). The expression of.Bmi-1 in CIN I, CIN II and CIN III was different (P < 0.05), and there was a difference between CIN I and CIN III (P < 0.05). The expression of Bmi-1 protein in cervical squamous cell carcinoma was related to the clinical stage, histological grade and lymph node metastasis (P < 0.05).
2, OPN expression: the expression of OPN protein in normal cervical tissue, CIN and cervical squamous cell carcinoma is mainly located in the cytoplasm and nucleus of.OPN in the normal cervix group, in the CIN group and in the cervical squamous cell carcinoma group, the overall difference is (P < 0.05), and the normal cervix group and the cervical squamous cell carcinoma group, the CIN group and the cervical squamous cell carcinoma group have a poor comparison. The expression of different (P < 0.05).OPN in CIN I, CIN II and CIN III was not different (P < 0.05), and there was no difference between 22 (P > 0.05). The expression of OPN protein in cervical squamous cell carcinoma was related to the clinical stage, histological grade, depth of tissue infiltration and lymph node metastasis (P < 0.05).
3, E-cadherin expression: the expression of E-cadherin protein in normal cervical tissue, CIN and cervical squamous cell carcinoma was mainly located in the cell membrane.E-cadherin in the normal cervix group, the CIN group and the cervical squamous cell carcinoma group gradually decreased (P < 0.05), and the ratio of 22 (P < 0.05) was different (P < 0.05).E-cadherin in CIN I, CIN II and CIN. There was no difference in expression in III (P < 0.05), and there was no difference in 22 of the differences (P > 0.05). In cervical squamous cell carcinoma, the expression of E-cadherin protein was related to the clinical stage, histological grade, depth of tissue infiltration and lymph node metastasis (P < 0.05).
4, Vimentin expression: Vimentin was not expressed in normal cervical tissues. The expression of Vimentin protein in the cytoplasm of CIN and cervical squamous cell carcinoma increased gradually in the cytoplasm and in the group of CIN and cervical squamous cell carcinoma (P < 0.05); in the normal cervix group and the cervical squamous cell carcinoma group, the CIN group and the cervical squamous cell carcinoma group. There was no significant difference in the expression of.Vimentin (P < 0.05) in CIN I, CIN II and CIN III (P < 0.05), and there was no statistically significant difference between 22 of them (P > 0.05). The expression of Vimentin protein in cervical squamous cell carcinoma was related to the depth of tissue infiltration, clinical stage and lymph node metastasis (P < 0.05).
5, the correlation of Bmi-1, OPN, E-cadherin and Vimentin in cervical squamous cell carcinoma:
The expression of Bmi-1 was negatively correlated with E-cadherin expression (r=-0.531, P < 0.05), and was positively correlated with the expression of Vimentin (r=0.344, P < 0.05).
(2) OPN and E-cadherin expression were negatively correlated (r=-0.544, P < 0.05), and positively correlated with Vimentin expression (r=0.368, P < 0.05).
There was a positive correlation between Bmi-1 and OPN expression (r=0.507, P < 0.05).
There was a negative correlation between E-cadherin and Vimentin expression (r=-0.341, P < 0.05).
conclusion
1, the high expression of proto oncogene Bmi-1 and tumor metastasis related gene OPN is closely related to the histological grade of cervical squamous cell carcinoma, clinical staging and lymph node metastasis, suggesting that Bmi-1, OPN may play an important role in the development of cervical squamous cell carcinoma and the process of invasion and metastasis.
2, Bmi-1 and OPN may promote the invasion and metastasis of cervical squamous cell carcinoma through epithelial mesenchymal transition.
3, there is a positive correlation between Bmi-1 and OPN expression in cervical squamous cell carcinoma, suggesting that both may promote the invasion and metastasis of cervical cancer.

【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.33

【參考文獻(xiàn)】

相關(guān)期刊論文 前6條

1 黃開紅;劉建化;李學(xué)先;宋立兵;曾木圣;;Bmi-1基因過度表達(dá)與胃癌分化、轉(zhuǎn)移及預(yù)后的關(guān)系[J];南方醫(yī)科大學(xué)學(xué)報(bào);2007年07期

2 胡中華;胡義德;朱勇;;非小細(xì)胞肺癌中Bmi-1表達(dá)情況的初步研究[J];中國(guó)肺癌雜志;2008年01期

3 李小磊;宋文杰;陳戰(zhàn);陳亞峰;李霄;周亮;張福琴;竇科峰;;siRNA沉默Bmi-1基因?qū)θ烁伟┘?xì)胞株MHCC97-H侵襲遷移能力的影響[J];世界華人消化雜志;2011年36期

4 丁凌,鄭樹,曹江;大腸癌及其肝轉(zhuǎn)移組織骨橋蛋白mRNA的表達(dá)[J];中華醫(yī)學(xué)雜志;2002年14期

5 ;Crosstalk between tumor cells and microenvironment via Wnt pathway in colorectal cancer dissemination[J];World Journal of Gastroenterology;2008年12期

6 ;Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells[J];World Journal of Gastroenterology;2008年16期

本文編號(hào)：1814167