本文選題：存活素 + 前列腺　； 參考：《南方醫(yī)科大學(xué)》2012年碩士論文

【摘要】：研究背景 前列腺癌(PCa)是一種嚴(yán)重影響老年男性生活質(zhì)量及預(yù)期壽命的疾病。隨著人們生活水平的不斷提高,前列腺癌的發(fā)病率亦日益增高。在歐洲和北美,其發(fā)病率及病死率分別位居男性惡性腫瘤的第2位及第6位。在我國,隨著人口老齡化、生活質(zhì)量的提高,生活方式改變諸多因素,前列腺癌的發(fā)病增長率已居泌尿生殖系惡性腫瘤之首。前列腺癌具有潛伏性,發(fā)病率高的特點,我國70歲以上男性人群中,高達(dá)25%的人患有前列腺癌,但發(fā)展到臨床癌者僅占極小部分。前列腺癌的主要檢測手段是前列腺特異性抗原(PSA),但血清PSA測定有局限性,診斷的敏感性與特異性欠理想,尤其對于檢測結(jié)果的灰區(qū)(4～10ng/ml,),常不易確診；在前列腺癌的治療方面,雖然方法較多,但均具有一定的局限性,化療藥物難以進(jìn)入前列腺癌組織,前列腺癌出現(xiàn)臨床癥狀時多已發(fā)生了轉(zhuǎn)移,手術(shù)治療效果差,內(nèi)分泌治療雖可改善患者癥狀,減輕病人痛苦,但對延長生存時間有限。前列腺癌臨床治療的最大難題在于對雄激素非依賴性前列腺癌缺乏有效的治療方案。分子生物學(xué)研究發(fā)現(xiàn)去勢治療、放療及某些化療藥物都是通過誘導(dǎo)前列腺癌細(xì)胞凋亡發(fā)揮作用。研究表明隨著細(xì)胞向惡性轉(zhuǎn)變,細(xì)胞的凋亡水平呈下降趨勢。目前對前列腺癌由雄激素依賴轉(zhuǎn)為雄激素非依賴(AIPC)的形成提出了兩種觀點：一是雄激素受體(AR)信號的增加促使雄激素受體增加,使AR對低水平雄激素或雌激素敏感增強(qiáng)甚至對雄激素阻斷劑敏感。另一種觀點認(rèn)為AIPC的形成是一種與AR無關(guān)的信號克服了凋亡,由此認(rèn)為凋亡信號的阻斷是腫瘤繼續(xù)生存的原因。前列腺癌的生長取決于細(xì)胞的增生率和死亡率之間的平衡,凋亡抑制蛋白在前列腺癌的發(fā)生中起著重要的作用。Survivin是新近發(fā)現(xiàn)的凋亡抑制蛋白(IAP)家族的成員。在眾多人類惡性腫瘤中上調(diào)表達(dá),并與腫瘤的凋亡、增殖、血管生成及其預(yù)后有密切關(guān)系,而在成人正常分化組織中不表達(dá)。Survivin很可能成為腫瘤診斷和治療的新靶點。目前,Survivin在前列腺癌中的表達(dá)及其意義的相關(guān)研究國內(nèi)外已有文獻(xiàn)報道,但結(jié)果不盡相同。因此,我們通過查閱大量國內(nèi)外文獻(xiàn),參考國內(nèi)外應(yīng)用免疫組織化學(xué)方法(S-P法)檢測Survivin在前列腺癌、正常前列腺及前列腺增生組織中表達(dá)的研究成果,進(jìn)一步系統(tǒng)評價Survivin與前列腺癌生物學(xué)行為之間的關(guān)系,期待為前列腺癌早期診斷提供一種新方法,為判斷前列腺癌的生物學(xué)行為提供新的手段,為前列腺癌的治療開辟一種新的途徑。目的 收集國內(nèi)外有關(guān)應(yīng)用免疫組織化學(xué)方法檢測Survivin在前列腺癌、正常前列腺及良性前列腺增生組織中表達(dá)的文獻(xiàn),通過Meta分析的方法比較Survivin在正常前列腺(NP)、良性前列腺增生(BPH)和前列腺癌(PCa)組織中的表達(dá),以及Survivin表達(dá)強(qiáng)度與前列腺癌(PCa)的臨床分期、病理分化、伴隨轉(zhuǎn)移是否存在臨床意義,旨在系統(tǒng)評價Survivin與前列腺癌的發(fā)生、發(fā)展等生物學(xué)行為的關(guān)系,為前列腺癌早期診斷提供一種新方法,為判斷前列腺癌的生物學(xué)行為提供新的手段,為前列腺癌的治療開辟一種新的途徑。 方法 1按系統(tǒng)評價要求制定相應(yīng)的詳細(xì)的納入與排除標(biāo)準(zhǔn),包括研究對象的特征、干預(yù)措施以及結(jié)局指標(biāo)的測量等。 2根據(jù)擬定的標(biāo)準(zhǔn)制定出系統(tǒng)、全面的檢索策略。計算機(jī)檢索MEDLINE、 Cochrane Library、CBM、CNKI數(shù)字圖書館、萬方數(shù)據(jù)庫、維普于(1997.1～2011.6)公開發(fā)表的原始文獻(xiàn)、會議論文集、畢業(yè)論文。采用主題詞與自由詞相結(jié)合的方式,所有檢索策略通過多次預(yù)檢索后確定。用Google等搜索引擎查找互聯(lián)網(wǎng)上的相關(guān)文獻(xiàn),輔以人工檢索并進(jìn)行文獻(xiàn)追溯。 3文獻(xiàn)的質(zhì)量評價及數(shù)據(jù)信息提�。河蓛晌辉u價者根據(jù)QUADAS (quality assessment of diagnostic accuracy studies)條目對納入研究質(zhì)量進(jìn)行獨(dú)立評價,如遇分歧通過討論或由第三位研究者協(xié)助解決。資料提取內(nèi)容包括①試驗的基本情況、兩組標(biāo)本的基線情況；②試驗設(shè)計、檢查方法、結(jié)局測量指標(biāo)、反應(yīng)研究質(zhì)量的指標(biāo)。 4資料的統(tǒng)計學(xué)處理：Revman5.1軟件進(jìn)行數(shù)據(jù)處理和分析。對提取所有計數(shù)資料效應(yīng)量均用比值比(Odds ratio,OR)及其95%可信區(qū)間(Confidence interval,CI)表示。研究間統(tǒng)計學(xué)異質(zhì)性檢驗采用卡方檢驗,以α=0.1為檢驗水準(zhǔn),以判斷多個研究結(jié)果的總體效應(yīng)是否一致。若多個研究結(jié)果的效應(yīng)一致,則采用固定效應(yīng)模型；反之,則用隨機(jī)效應(yīng)模型。對可能影響合并效應(yīng)的不同人種因素采用敏感性分析,從而判斷結(jié)果的穩(wěn)定性和強(qiáng)度。 結(jié)果 1資料概括本研究共納入18項研究。18篇診斷對照研究經(jīng)文獻(xiàn)質(zhì)量評價均為高質(zhì)量文獻(xiàn)。共1387例前列腺標(biāo)本,正常前列腺(NP)標(biāo)本133例、前列腺增生(BPH)標(biāo)本402例、前列腺癌(PCa)標(biāo)本852例。其中9篇文獻(xiàn)行前列腺癌與正常前列腺組織比較；16篇文獻(xiàn)行前列腺癌與良性前列腺增生比較；14篇涉及不同分化程度Survivin表達(dá)的比較；11篇涉及不同臨床分期的比較；6篇行伴隨轉(zhuǎn)移與否情況下前列腺癌組織Survivin表達(dá)陽性的比較。 2Meta分析結(jié)果2.1對前列腺癌與正常前列腺Survivin表達(dá)陽性比較：9項研究進(jìn)行Meta分析,異質(zhì)性檢驗(χ2=4.48,P=0.810,12=0%)采用固定效應(yīng)模型,結(jié)果顯示,前列腺癌陽性率66.20%(296/454),正常前列腺陽性率3.0%(4/133),OR值47.23,95%CI(20.00,111.56),兩組陽性率差別有統(tǒng)計學(xué)意義(P0.001)提示Survivin在前列腺癌的表達(dá)顯著強(qiáng)于正常前列腺組織。 2.2前列腺癌與良性前列腺增生Survivin表達(dá)陽性比較：16項研究進(jìn)行Meta分析,異質(zhì)性檢驗,(χ2=44.99,P0.001,12=67%),采用隨機(jī)效應(yīng)模型,結(jié)果顯示,前列腺癌陽性率67.67%(519/767),良性前列腺增生陽性率11.44%(46/402),OR值21.25,95%CI(10.32,43.75),兩組陽性表達(dá)率差異有統(tǒng)計學(xué)意義(P0.001),提示Survivin在前列腺癌表達(dá)較良性前列腺增生顯著增強(qiáng)。 2.3前列腺高分化癌組織與低分化癌組織Survivin表達(dá)陽性比較：14項研究進(jìn)行Meta分析,異質(zhì)性檢驗,(χ2=17.13,P=0.190,I2=24%),采用固定效應(yīng)模型,結(jié)果顯示,前列腺高分化癌陽性率52.66%(99/188),低分化癌陽性率89.66%(182/203),OR值0.11,95%CI(0.06,0.20),兩組陽性表達(dá)率差異有統(tǒng)計學(xué)意義(P0.001),提示Survivin在前列腺高分化癌組織表達(dá)較低分化癌組織的表達(dá)顯著降低。 2.4Survivin在臨床A+B期與C+D期前列腺癌組織表達(dá)的陽性比較：11項研究進(jìn)行Meta分析,異質(zhì)性檢驗,(χ2=6.40,P=0.780,12=0%),采用固定效應(yīng)模型,結(jié)果顯示,臨床A+B期前列腺癌陽性率65.43%(159/243),C+D期癌組織的表達(dá)陽性率91.77%(223/243),OR值0.14,95%CI(0.08,0.26),兩組陽性表達(dá)率比較有統(tǒng)計學(xué)意義(P0.001),提示Survivin蛋白在前列腺癌臨床A+B期與C+D期癌組織的表達(dá)陽性率有顯著差異。 2.5伴轉(zhuǎn)移與非轉(zhuǎn)移前列腺癌組織Survivin陽性表達(dá)率比較：對6項研究進(jìn)行Meta分析,異質(zhì)性檢驗(χ2=5.73,P=0.330,12=13%),采用固定效應(yīng)模型,結(jié)果顯示,伴隨轉(zhuǎn)移前列腺癌陽性率90.48%(95/105),非轉(zhuǎn)移前列腺癌陽性率62.50%(120/192),OR值5.76,95%CI(2.81,11.84),兩組陽性表達(dá)率比較有統(tǒng)計學(xué)意義(P0.001),提示Survivin蛋白在伴有淋巴結(jié)或全身他處轉(zhuǎn)移較非轉(zhuǎn)移的前列腺癌組織的表達(dá)陽性率顯著增強(qiáng)。 結(jié)論 前列腺癌Survivin表達(dá)明顯高于正常前列腺及良性前列腺增生；且Survivin在前列腺癌組織的表達(dá)與腫瘤病理分化,臨床分期,是否伴隨轉(zhuǎn)移明顯相關(guān),提示Survivin表達(dá)陽性越高,前列腺癌發(fā)生的機(jī)率越高,越具有侵襲性,腫瘤的預(yù)后越差。因此Survivn檢測可作為前列腺癌早期診斷提供一種新方法,為判斷前列腺癌的生物學(xué)行為提供新的手段,為前列腺癌的基因治療開辟一種新的途徑。
[Abstract]:Research background
Prostate cancer (PCa) is a disease that seriously affects the life quality and life expectancy of old men. With the continuous improvement of people's living standards, the incidence of prostate cancer is also increasing. In Europe and North America, the incidence and mortality rate are the second and 6 in male malignant tumors. In our country, with the aging of the population, life is in China. The increase of quality and lifestyle changes many factors, the incidence of prostate cancer has been the first of the malignant tumor of the genitourinary system. Prostate cancer is latent and the incidence is high. In the male population over 70 years old, up to 25% of the people have prostate cancer, but only a small part of the cancer is developed to the clinical cancer. The detection method is prostate specific antigen (PSA), but the determination of serum PSA is limited, the sensitivity and specificity of diagnosis are not ideal, especially in the grey area (4 ~ 10ng/ml) of the test results, it is often difficult to diagnose. Although there are many methods in the treatment of prostate cancer, they are all limited, and the chemotherapeutic drugs are difficult to enter the prostate cancer. The most difficult problem in the clinical treatment of prostate cancer is the lack of effective treatment for androgen independent prostate cancer. The study found that castration, radiotherapy and some chemotherapeutic agents play a role in inducing apoptosis in prostate cancer cells. The study showed that the apoptosis level of the cells decreased as the cell turned to malignant transformation. Two views on the formation of prostate cancer from androgen dependence to androgens (AIPC) were proposed: first, male irritable. An increase in the hormone receptor (AR) signal causes an increase in androgen receptor, which makes AR sensitive to low androgen or estrogen sensitivity and is sensitive to androgen blockade. Another view is that the formation of AIPC is a AR independent signal that overcomes apoptosis, thus suggesting that the blocking of apoptotic signals is the cause of the tumor's continued survival. Prostate cancer Growth depends on the balance between the proliferation rate and death rate of the cells. The apoptosis inhibitory protein plays an important role in the development of prostate cancer..Survivin is a member of the newly discovered family of apoptosis suppressor (IAP). It is up-regulated in a large number of human malignant tumors and is closely related to the apoptosis, proliferation, angiogenesis and prognosis of the tumor. The non expression of.Survivin in normal adult tissues is likely to be a new target for the diagnosis and treatment of cancer. At present, the related research on the expression and significance of Survivin in prostate cancer has been reported at home and abroad, but the results are not the same. Therefore, we refer to a large number of domestic and foreign literature and refer to the exemption from domestic and foreign applications. The research results of the expression of Survivin in prostate cancer, normal prostate and prostatic hyperplasia tissue were detected by S-P method. The relationship between Survivin and biological behavior of prostate cancer was evaluated systematically, and a new method for the early diagnosis of prostate cancer was expected to provide a new method to judge the biological behavior of prostate cancer. New means of opening up a new way for the treatment of prostate cancer.
The literature on the expression of Survivin in prostate cancer, normal prostate and benign prostatic hyperplasia tissue was collected at home and abroad, and the expression of Survivin in normal prostate (NP), benign prostatic hyperplasia (BPH) and anterior adenocarcinoma (PCa) tissue was compared by Meta analysis, and the expression intensity of Survivin was compared. The clinical staging of prostate cancer (PCa), pathological differentiation and the clinical significance of metastasis are designed to systematically evaluate the relationship between Survivin and the occurrence and development of prostate cancer, to provide a new method for the early diagnosis of prostate cancer, and to provide a new method for judging the biological behavior of prostate cancer and the treatment of prostate cancer. The treatment opens up a new way.
Method
1 according to the requirements of systematic review, the detailed inclusion and exclusion criteria should be worked out, including the characteristics of subjects, intervention measures and the measurement of outcome indicators.
2 according to the proposed standards, a system, a comprehensive retrieval strategy. Computer retrieval of MEDLINE, Cochrane Library, CBM, CNKI digital library, Wanfang database, VP in the (1997.1 to 2011.6) published original documents, conference papers, graduation thesis. After the pre examination, it will be identified. Search engines on the Internet will be searched by Google and other search engines, supplemented by manual retrieval and literature review.
3 literature quality evaluation and data information extraction: two evaluators based on the QUADAS (quality assessment of diagnostic accuracy studies) entry for the independent evaluation of the quality of the study, such as in the case of disagreement through discussion or by the assistance of third researchers. The content of data extraction includes the basic conditions of the test and the two groups of specimens Baseline conditions; 2. Test design, examination methods, outcome measures, and indicators of response research quality.
4 data processing: Revman5.1 software for data processing and analysis. The ratio Ratio ratio (Odds ratio, OR) and its 95% confidence interval (Confidence interval, CI) were used to extract all the count data. Statistical heterogeneity test was used in Chi square test and alpha =0.1 as the test level to judge the general results of multiple research. If the effect of the body effect is consistent. If the effects of the results are the same, the fixed effect model is used. On the contrary, the random effect model is used to analyze the different human factors that may affect the combination effect, so as to determine the stability and intensity of the results.
Result
1 a total of 18 studies were included in the study. The quality evaluation of the.18 diagnosis was high quality literature. There were 1387 cases of prostate specimens, 133 normal prostate (NP) specimens, 402 cases of benign prostatic hyperplasia (BPH), and 852 cases of prostate cancer (PCa). 9 literature compared the prostate cancer to the normal prostate tissue; 16 articles were compared with the normal prostate tissue. The literature was compared with benign prostatic hyperplasia in the literature; 14 articles were compared with the Survivin expression of different degrees of differentiation; 11 were compared to different clinical stages, and the positive of Survivin in the prostate cancer tissue was compared in the 6 cases.
2Meta analysis results 2.1 positive prostate cancer and normal prostate Survivin expression positive: 9 studies performed Meta analysis, heterogeneity test (chi 2=4.48, P=0.810,12=0%) using the fixed effect model, the results showed that the positive rate of prostate cancer was 66.20% (296/454), normal prostaglandin gland positive rate 3% (4/133), OR value 47.23,95%CI (20.00111.56), two groups of Yang. The difference in sex ratio was statistically significant (P0.001), suggesting that the expression of Survivin in prostate cancer was significantly stronger than that in normal prostate tissue.
2.2 positive comparison of Survivin expression in prostate cancer and benign prostatic hyperplasia: 16 studies performed Meta analysis, heterogeneity test, (x 2=44.99, P0.001,12=67%), using random effect model. The results showed that the positive rate of prostate cancer was 67.67% (519/767), benign prostatic growth positive rate 11.44% (46/402), OR value 21.25,95%CI (10.32,43.75), two groups of Yang. The difference of sex expression rate was statistically significant (P0.001), suggesting that Survivin expression in prostate cancer was significantly higher than that in benign prostatic hyperplasia.
2.3 the positive comparison of Survivin expression in highly differentiated prostate cancer tissue and low differentiated carcinoma tissue: 14 studies performed Meta analysis, heterogeneity test, (x 2=17.13, P=0.190, I2=24%), using the fixed effect model. The results showed that the positive rate of high differentiated prostate cancer was 52.66% (99/188), the positive rate of low differentiated carcinoma (182/203), OR value 0.11,95%CI (0.06,0.20), The positive expression rate of the two groups was statistically significant (P0.001), indicating that Survivin expression was significantly reduced in poorly differentiated cancer tissues.
The positive comparison of the expression of 2.4Survivin in phase A+B and C+D stage prostate cancer tissue: 11 studies performed Meta analysis, heterogeneity test, (x 2=6.40, P=0.780,12=0%), using the fixed effect model. The results showed that the positive rate of prostate cancer in A+B phase was 65.43% (159/243), the positive rate of C+D stage carcinoma tissue was 91.77% (223/243), OR 0.14,95%CI (0) .08,0.26), the positive expression rate of the two groups was statistically significant (P0.001), suggesting that the positive rate of Survivin protein in the A+B and C+D stage of prostate cancer was significantly different.
The positive rate of positive expression of Survivin in 2.5 and non metastatic prostate cancer tissues: 6 studies were analyzed by Meta, heterogeneity test (x 2=5.73, P=0.330,12=13%), using the fixed effect model. The results showed that the positive rate of the adjoint metastatic prostate cancer was 90.48% (95/105), the positive rate of non metastatic prostate cancer was 62.50% (120/192), and OR value 5.76,95%CI (2.81,1). 1.84) the positive rate of the two groups was statistically significant (P0.001), suggesting that the positive rate of Survivin protein expression was significantly enhanced in the metastatic prostate cancer tissue with lymph node or whole body metastasis.
conclusion
The expression of Survivin in prostate cancer is significantly higher than that of normal prostate and benign prostatic hyperplasia; and the expression of Survivin in the prostate cancer tissue is associated with the pathological differentiation of the tumor, and the clinical stages are associated with the metastasis. The higher the expression of Survivin is, the higher the probability of the prostate cancer, the more invasive, the worse the prognosis of the tumor. This Survivn detection can provide a new method for the early diagnosis of prostate cancer. It provides a new way to judge the biological behavior of prostate cancer and opens a new way for the gene therapy of prostate cancer.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R737.25

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相關(guān)碩士學(xué)位論文 前4條

1 張劍;Survivin在前列腺癌組織中的表達(dá)及其意義[D];第四軍醫(yī)大學(xué);2005年

2 楊文峰;存活素Survivin在前列腺癌中的表達(dá)及意義[D];中國醫(yī)科大學(xué);2006年

3 陳平鋒;Survivin和VEGF在前列腺癌組織中的表達(dá)及意義[D];南華大學(xué);2006年

4 劉鎖民;Survivin和FasL在前列腺癌中的表達(dá)及其意義[D];中國醫(yī)科大學(xué);2007年

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