本文選題：前列腺癌　切入點：細胞自噬　出處：《安徽醫(yī)科大學》2015年碩士論文　論文類型：學位論文

【摘要】：細胞自噬(Autophagy)是一個廣泛存在于真核細胞中的重要的生理過程,主要方式為細胞初級溶酶體處理內(nèi)源性底物,包括細胞清除廢物、重建結(jié)構以及生長發(fā)育。生命體借此維持蛋白代謝平衡及細胞內(nèi)環(huán)境穩(wěn)定,并與疾病的發(fā)生密切相關。目前,學術界公認的自噬主要形式有:巨自噬(macroautophagy),微自噬(microautophagy),以及分子伴侶介導的自噬(chaperone mediated autophagy,CMA)。巨自噬即是我們通常所稱的自噬。目前已知的自噬調(diào)控途徑有:Beclin-1信號途徑;mTOR(Mammalian Target of Rapamycin)信號途徑;自噬相關基因(Autophagy Related Gene,Atg)與泛素樣結(jié)合系統(tǒng)(Ubiquitin-link system)。其中,自噬基因Beclin-1與酵母自噬基因Atg6同源,位于染色體17q21,定位于高爾基體參與哺乳動物自噬體的形成,是介導其他自噬蛋白定位于前自噬小體的關鍵因子。前列腺癌(Prostate Cancer,PCa)是當今社會常見的男性惡性腫瘤。近年來,其發(fā)病率在我國男性人群中呈逐年攀高趨勢。晚期前列腺癌的治療大多依賴于去除雄激素方法。然而,絕大多數(shù)患者最終會轉(zhuǎn)變?yōu)樾奂に氐挚剐颓傲邢侔?Castrate-Resistant Prostate Cancer,CRPC),導致對傳統(tǒng)的去勢治療反應效果不佳。相關研究已經(jīng)初步證明自噬在CRPC中扮演著重要角色,而自噬基因Beclin-1在多種腫瘤組織中呈低水平表達,預示著細胞自噬在前列腺癌的發(fā)生、發(fā)展、轉(zhuǎn)歸中發(fā)揮著作用。本課題采用免疫組化的方法檢測Beclin-1在前列腺癌組織中的表達并探討其與相關臨床、病理因素的關系。本研究取用經(jīng)直腸前列腺穿刺活檢術后的病理標本,共132例,所有標本均經(jīng)病理證實為前列腺腺癌。本研究實驗組即為前列腺腺癌組織,對照組即為良性前列腺增生組織。納入研究的每例標本均至少有一針為良性前列腺增生組織(即癌旁組織)。對132例患者的全部穿刺標本行免疫組化染色,若其中有任何一針染色呈陽性表達,即可納入相應的陽性組;若全部為陰性表達,則納入相應的陰性組。采用免疫組化Super Vision兩步法檢測132例前列腺癌組織及癌旁組織中Beclin-1的表達,并分析其與相關臨床因素的關系。結(jié)果發(fā)現(xiàn):1.Beclin-1染色陽性物質(zhì)呈棕黃色,表達位于細胞漿。在132例前列腺穿刺活檢的病理組織中,癌旁組織的Beclin-1陽性表達率為54.5%,腫瘤組織的Beclin-1陽性表達率為38.6%,明顯低于其在癌旁組織中的表達。2.本研究將132例前列腺癌穿刺標本按術后Gleason評分不同分為三組:2~4分;5~7分;8分以上。Beclin-1在三組中的陽性表達率分別為66.7%,39.7%,27.3%,評分越高,表達率越低,組間差異具有統(tǒng)計學意義。3.Beclin-1的表達差異與是否發(fā)生淋巴結(jié)轉(zhuǎn)移、是否發(fā)生骨轉(zhuǎn)移有關,具有統(tǒng)計學意義(P0.05);而與年齡、是否具有家族史及前列腺炎病史差異均無統(tǒng)計學意義(P0.05)。4.在全部132例前列腺癌患者中,有76例進行了根治性前列腺切除術,術后三個月進行隨訪,檢測PSA水平,有10例≥0.02ng/ml,66例0.02ng/ml。在PSA0.02ng/ml的66例中有42例Beclin-1表達陽性,陽性率為63.6%,而在PSA≥0.02ng/ml的10例中,2例Beclin-1表達為陽性,陽性率為20%,明顯低于前者(P0.05)。以上研究提示,自噬基因Beclin-1在前列腺癌組織中表達下調(diào),并與淋巴結(jié)轉(zhuǎn)移、骨轉(zhuǎn)移及生化復發(fā)有關,其表達下調(diào)可能參與前列腺癌的發(fā)生、發(fā)展,為前列腺癌的診斷及治療提供了新的思路。
[Abstract]:Autophagy (Autophagy) is a widespread important physiological processes in eukaryotic cells, the main way for cell lysosomes processing endogenous substrates, including the removal of waste cells, reconstruction of structure and growth life. To maintain the balance of protein metabolism and cell homeostasis, and is closely related with the occurrence of the disease at present. Autophagy, mainly in the form of academic circles have been recognized: macroautophagy (macroautophagy), microautophagy (microautophagy), as well as molecular chaperone mediated autophagy (chaperone mediated, autophagy, CMA). The giant autophagy is that we are often called autophagy. Currently autophagy pathways known: Beclin-1 signaling pathway; mTOR (Mammalian Target of Rapamycin) signaling pathway of autophagy related genes (Autophagy, Related; Gene, Atg) system combined with ubiquitin like (Ubiquitin-link system). Among them, the autophagy gene Beclin-1 and yeast from Phage Atg6 homologous gene, located on chromosome 17q21, forming localized in the Golgi in mammalian autophagy, is a key factor mediated autophagy protein located in the other before the autophagosome. Prostate cancer (Prostate Cancer PCa) is a common malignant tumor in male society. In recent years, the incidence in the male population in China was gradually rising trend. In the treatment of advanced prostate cancer mainly depends on androgen removal methods. However, most patients eventually transformed into androgen resistant prostate cancer (Castrate-Resistant Prostate Cancer, CRPC), resulting in the effect of castration in response to the traditional poor. Studies have proved that autophagy plays an important role in CRPC, and autophagy gene Beclin-1 in various tumor tissues showed low expression indicates that autophagy in prostate carcinogenesis, development, to play a role Expression. The method of immunohistochemical detection of Beclin-1 in prostate cancer tissues and to explore its relationship with clinical and pathological factors. This study used by pathology after transrectal prostate biopsy, a total of 132 cases, all specimens were pathologically confirmed prostate adenocarcinoma in this research. The experimental group is prostate adenocarcinoma, the control group is the benign prostatic hyperplasia. Every case were included in the study were at least one needle for benign prostatic hyperplasia (i.e. carcinoma). With the color of 132 patients with biopsy specimens of all immune groups, if there is any one positive expression that can be put into the corresponding positive group; if all the negative, are included in the negative group. The corresponding expression of Beclin-1 Super Vision two step method for detection of prostate cancer and 132 cases of carcinoma tissues, and analyze the The relationship and clinical factors. The results showed that 1.Beclin-1 positive staining material was brown, expression located in the cytoplasm. In 132 cases of pathological biopsy of the prostate, the positive expression of Beclin-1 in tissue adjacent to carcinoma was 54.5%, the positive expression of Beclin-1 in tumor tissues was 38.6%, was significantly lower than that in the adjacent tissues the expression of.2. in this study, 132 cases of prostate cancer biopsy specimens according to postoperative Gleason score were divided into three groups: 2~4; 5~7; expression of more than 8.Beclin-1 in the three groups in the rates were 66.7%, 39.7%, 27.3%, the higher the score, the expression rate is low, the difference between the groups was statistically difference expression the significance of.3.Beclin-1 and incidence of lymph node metastasis, whether the occurrence of bone metastasis, with statistical significance (P0.05); and whether there is difference with age, medical history and family history of prostatitis were not statistically significant (P0.05.4.) in all 132 Patients with prostate cancer, 76 cases of radical prostatectomy were followed up three months after operation, testing the levels of PSA, 10 cases of more than 0.02ng/ml and 0.02ng/ml. in 66 cases in PSA0.02ng/ml 66 cases in 42 cases of Beclin-1 positive expression, the positive rate was 63.6%, while in PSA over 0.02ng /ml 10 in the cases, 2 cases of positive Beclin-1 expression, the positive rate was 20%, significantly lower than the former (P0.05). These studies suggest that expression of autophagy gene Beclin-1 in prostate cancer with lymph node metastasis and reduction, bone metastasis and biochemical recurrence is related to the down-regulation of its expression may be involved in prostate carcinogenesis, development, provide new ideas for the diagnosis and treatment of prostate cancer.

【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R737.25

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