本文關(guān)鍵詞： 卵巢癌 子宮內(nèi)膜癌 人附睪蛋白4(HE4)　出處：《中國(guó)人民解放軍醫(yī)學(xué)院》2016年博士論文　論文類型：學(xué)位論文

【摘要】：研究背景：卵巢癌和子宮內(nèi)膜癌是婦科常見(jiàn)惡性腫瘤,早期診斷、早期治療、規(guī)范隨訪是改善預(yù)后的重要手段。CA125是目前應(yīng)用最廣泛的腫瘤標(biāo)志物,但它在許多婦科良性疾病和內(nèi)科疾病中也升高,用于診斷癌癥的特異性不佳。HE4是由Kirchhoff于1991年從人的附睪遠(yuǎn)端上皮細(xì)胞中發(fā)現(xiàn)的,因其在惡性腫瘤組織中的特異性高表達(dá)正受到越來(lái)越多的關(guān)注。HE4作為卵巢癌血清標(biāo)記物被認(rèn)為要優(yōu)于CA125,在子宮內(nèi)膜癌早期診斷及預(yù)后判斷方面也發(fā)揮重要的作用。目的：觀察卵巢良性腫瘤、卵巢上皮性癌、子宮內(nèi)膜癌患者血清和組織中CA1 25及HE4水平,并分析其在各組病例中的表達(dá)情況以及臨床意義。通過(guò)RNA干擾技術(shù)觀察HE4基因沉默對(duì)腫瘤細(xì)胞增殖、轉(zhuǎn)移及侵蝕能力的影響。建立卵巢細(xì)胞系CaoV3裸鼠皮下移植瘤模型,體內(nèi)觀察HE4低表達(dá)對(duì)腫瘤生長(zhǎng)的影響,以初步探求HE4與卵巢癌及子宮內(nèi)膜癌發(fā)生的關(guān)系材料與方法：1、收集卵巢上皮性癌、良性上皮性卵巢腫瘤患者和子宮內(nèi)膜癌患者術(shù)前血清,檢測(cè)血清CA 125及HE4蛋白的表達(dá)水平,并分析其在腫瘤診斷中的靈敏度及特異度。2、收集卵巢上皮性癌、良性上皮性卵巢腫瘤患者和子宮內(nèi)膜癌患者組織,檢測(cè)組織中HE4蛋白的表達(dá)情況,分析其與腫瘤臨床病理特征的相關(guān)性。3、構(gòu)建shRNA-HE4慢病毒載體,轉(zhuǎn)染到CaoV3細(xì)胞,觀察HE4基因沉默對(duì)CaoV3增殖、轉(zhuǎn)移及侵蝕能力的影響。4、建立CaoV3裸鼠皮下移植瘤模型,體內(nèi)觀察shRNA-HE4對(duì)卵巢癌腫瘤生長(zhǎng)的影響。結(jié)果：1、血清HE4在卵巢癌高于健康對(duì)照組及良性腫瘤組,HE4診斷卵巢癌的特異度高于CA125。HE4水平與卵巢癌期別及淋巴轉(zhuǎn)移相關(guān)。子宮內(nèi)膜癌組HE4水平高于健康對(duì)照組及子宮內(nèi)膜增生組,但與腫瘤分期等病理特征無(wú)相關(guān)性。2、組織中卵巢癌HE4表達(dá)陽(yáng)性率高于卵巢良性腫瘤組,與卵巢癌期別及淋巴結(jié)轉(zhuǎn)移相關(guān)。子宮內(nèi)膜癌組HE4表達(dá)陽(yáng)性率高于健康對(duì)照組及子宮內(nèi)膜增生組,與淋巴結(jié)轉(zhuǎn)移有關(guān)。3、成功構(gòu)建HE4 shRNA慢病毒,并獲得穩(wěn)定表達(dá)的細(xì)胞株。敲低HE4基因后,細(xì)胞株增殖顯著減慢,細(xì)胞周期出現(xiàn)G0/G1阻滯。4、HE4基因沉默能抑制腫瘤細(xì)胞在裸鼠體內(nèi)的生長(zhǎng),抑制裸鼠腫瘤的體積,與對(duì)照組有顯著性差異。結(jié)論：1、與CA125相比,HE4對(duì)于卵巢上皮性癌及子宮內(nèi)膜癌有更好的診斷價(jià)值。2、HE4基因參與促進(jìn)癌細(xì)胞的增殖、遷移、侵襲等行為。3、HE4基因沉默顯著抑制卵巢癌細(xì)胞株在裸鼠體內(nèi)的生長(zhǎng)。
[Abstract]:Background: ovarian cancer and endometrial carcinoma are common malignant tumors in gynecology. Early diagnosis, early treatment and standardized follow-up are important means to improve prognosis. CA125 is the most widely used tumor marker. However, it is also elevated in many benign gynecological and internal diseases, and the poor specificity for the diagnosis of cancer. HE4 was found in human epididymal distal epithelial cells in 1991 by Kirchhoff. Because of its specific high expression in malignant tumor tissues, more and more attention has been paid to HE4 as a serum marker of ovarian cancer, which is considered to be superior to CA125. It also plays an important role in early diagnosis and prognosis of endometrial carcinoma. Objective: to observe benign ovarian tumor and epithelial ovarian carcinoma. The levels of CA1 25 and HE4 in serum and tissue of patients with endometrial carcinoma. The expression and clinical significance of HE4 gene silencing in each group were analyzed. The effect of HE4 gene silencing on tumor cell proliferation was observed by RNA interference technique. Establishment of ovarian cell line CaoV3 nude mice subcutaneous transplanted tumor model in vivo to observe the effect of low expression of HE4 on tumor growth. Methods: to investigate the relationship between HE4 and ovarian cancer and endometrial carcinoma. The serum samples were collected from patients with ovarian epithelial carcinoma, benign epithelial ovarian tumor and endometrial carcinoma before operation. The expression of CA125 and HE4 protein in serum was detected, and the sensitivity and specificity of CA125 and HE4 protein in the diagnosis of ovarian epithelial carcinoma were analyzed. The expression of HE4 protein in benign epithelial ovarian tumor and endometrial carcinoma was detected, and the correlation between the expression of HE4 protein and clinicopathological features of the tumor was analyzed. ShRNA-HE4 lentivirus vector was constructed and transfected into CaoV3 cells. The effect of HE4 gene silencing on the proliferation, metastasis and erosion of CaoV3 was observed. The effect of shRNA-HE4 on the growth of ovarian cancer was observed in vivo. Results the serum HE4 in ovarian cancer was higher than that in healthy control group and benign tumor group. The specificity of HE4 in diagnosis of ovarian cancer was higher than that of CA125.HE4, and the level of HE4 in endometrial carcinoma group was higher than that in healthy control group and endometrial hyperplasia group. The positive rate of HE4 expression in ovarian cancer was higher than that in benign ovarian tumors. The positive rate of HE4 expression in endometrial carcinoma group was higher than that in healthy control group and endometrial hyperplasia group, and was related to lymph node metastasis. HE4 shRNA lentivirus was successfully constructed and stably expressed cell lines were obtained. After knockout of HE4 gene, cell proliferation was significantly decreased and cell cycle was arrested by G _ 0 / G _ 1 arrest. HE4 gene silencing could inhibit the growth of tumor cells and tumor volume in nude mice, which was significantly different from that in control group. Conclusion: 1, compared with CA125, the silencing of HE4 gene can inhibit the growth of tumor cells in nude mice. HE4 has better diagnostic value for epithelial ovarian carcinoma and endometrial carcinoma. 2HE4 gene plays an important role in promoting the proliferation, migration and invasion of cancer cells. HE4 gene silencing significantly inhibited the growth of ovarian cancer cell line in nude mice.
【學(xué)位授予單位】：中國(guó)人民解放軍醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R737.3

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