【摘要】：目的:通過(guò)檢測(cè)ING4、P53、Ki-67、Fas/Fas L在膀胱尿路上皮癌中的表達(dá)變化,探討ING4、P53、Ki-67、Fas/Fas L在膀胱尿路上皮癌發(fā)生發(fā)展中的作用和臨床意義,分析ING4與P53、Ki-67、Fas/Fas L之間的相互關(guān)系,并對(duì)膀胱癌的標(biāo)記物、基因治療、早期診斷、術(shù)后隨訪及預(yù)后判斷提供一定的理論基礎(chǔ)。方法:收集川北醫(yī)學(xué)院附屬醫(yī)院和南充市中心醫(yī)院2014~2015年經(jīng)手術(shù)切除的并有完整臨床資料的膀胱尿路上皮癌標(biāo)本60例,癌旁組織60例,膀胱正常黏膜組織37例。采用免疫組織化學(xué)Elivsion TMPlus二步法檢測(cè)ING4、P53、Ki-67、Fas及Fas L在膀胱尿路上皮癌、癌旁組織及膀胱正常黏膜組織中的表達(dá)。結(jié)果:1.ING4在膀胱尿路上皮癌的陽(yáng)性表達(dá)率70%(42/60),在癌旁組織的陽(yáng)性表達(dá)率100%(60/60),在正常膀胱黏膜組織中的陽(yáng)性表達(dá)率97.2%(36/37),膀胱尿路上皮癌的陽(yáng)性表達(dá)率低于膀胱正常黏膜組織和癌旁組織,差異有統(tǒng)計(jì)學(xué)意義(P0.05),正常膀胱黏膜組織與癌旁組織的陽(yáng)性表達(dá)率差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。隨著病理級(jí)別的分化程度或臨床分期的增高,ING4在膀胱尿路上皮癌中的表達(dá)呈下降趨勢(shì)(P0.05)。2.P53在膀胱尿路上皮癌的陽(yáng)性表達(dá)率96.7%(58/60),在癌旁組織中的陽(yáng)性表達(dá)率13.3%(8/60),在膀胱正常黏膜組織中的陽(yáng)性表達(dá)率中13.5%(5/37),膀胱尿路上皮癌的陽(yáng)性表達(dá)率高于膀胱正常黏膜組織和癌旁組織(P0.05),膀胱正常黏膜組織與癌旁組織的陽(yáng)性表達(dá)率差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。隨著病理級(jí)別的分化程度或臨床分期增高,P53在膀胱尿路上皮癌中的表達(dá)呈上升趨勢(shì)(P0.05)。P53在多發(fā)的膀胱尿路上皮癌的的陽(yáng)性表達(dá)率高于單發(fā)的膀胱尿路上皮癌(P0.05)。3.Ki-67在膀胱尿路上皮癌的陽(yáng)性表達(dá)率91.7%(55/60),在癌旁組織中的陽(yáng)性表達(dá)率11.7%(7/60),在膀胱正常黏膜組織中的陽(yáng)性表達(dá)率2.7%(1/37),膀胱尿路上皮癌的陽(yáng)性表達(dá)率高于膀胱正常黏膜組織和癌旁組織(P0.05),膀胱正常黏膜組織與癌旁組織的陽(yáng)性表達(dá)率差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。隨著病理級(jí)別的分化程度或臨床分期增高,Ki-67在膀胱尿路上皮癌中的表達(dá)呈上升趨勢(shì)(P0.05),Ki-67在多發(fā)的膀胱尿路上皮癌的的陽(yáng)性表達(dá)率高于單發(fā)的膀胱尿路上皮癌(P0.05)。4.Fas在膀胱尿路上皮癌的陽(yáng)性表達(dá)率70%(42/60),在癌旁組織中的陽(yáng)性表達(dá)率88.3%(53/60),在膀胱正常黏膜組織中的陽(yáng)性表達(dá)率89.2%(34/37),膀胱正常黏膜組織和癌旁組織的陽(yáng)性表達(dá)率高于膀胱尿路上皮癌(P0.05),膀胱正常黏膜組織與癌旁組織的陽(yáng)性表達(dá)率差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。隨著病理級(jí)別增高,Fas在膀胱尿路上皮癌中的表達(dá)呈下降趨勢(shì)(P0.05)。5.Fas L在膀胱尿路上皮癌的陽(yáng)性表達(dá)率76.7%(46/60),在癌旁組織中的陽(yáng)性表達(dá)率100%(60/60),在膀胱正常黏膜組織中的陽(yáng)性表達(dá)率94.6%(35/37),膀胱尿路上皮癌的陽(yáng)性表達(dá)率低于膀胱正常黏膜組織和癌旁組織(P0.05),膀胱正常黏膜組織與癌旁的陽(yáng)性表達(dá)率差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。6.應(yīng)用Spearman等級(jí)相關(guān)性分析ING4與P53、Ki-67、Fas/Fas L之間的關(guān)系。ING4與P53、Ki-67呈負(fù)相關(guān),ING4與Fas/Fas L呈正相關(guān),相關(guān)性具有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:1.ING4在膀胱尿路上皮癌中的低表達(dá)或缺失,提示ING4在膀胱尿路上皮癌中起抑制作用。隨著膀胱癌的臨床分期或病理分級(jí)增高呈下降趨勢(shì),提示ING4與腫瘤的侵襲性存在緊密的關(guān)系,說(shuō)明ING4可成為預(yù)測(cè)膀胱腫瘤進(jìn)展的相對(duì)可靠的臨床指標(biāo)之一。2.P53在膀胱尿路上皮癌中的高表達(dá),并隨著膀胱癌的臨床分期或病理分級(jí)及腫瘤個(gè)數(shù)增高呈上升趨勢(shì),提示P53蛋白的過(guò)度表達(dá)是膀胱癌高度惡性的標(biāo)志之一。3.Ki-67在膀胱尿路上皮癌中的高表達(dá),并隨著膀胱尿路上皮癌的臨床分期或病理分級(jí)及腫瘤個(gè)數(shù)增高呈上升趨勢(shì),提示Ki-67可以成為膀胱癌發(fā)生發(fā)展、診斷及預(yù)后的良好指標(biāo)之一,并對(duì)預(yù)測(cè)膀胱癌的早期復(fù)發(fā)、惡化及治療效果的判定有重要的臨床意義。4.Fas在膀胱尿路上皮癌中的低表達(dá)及缺失,提示膀胱腫瘤可抵制由Fas介導(dǎo)的凋亡途徑從而對(duì)腫瘤進(jìn)展產(chǎn)生重要的影響。因此檢測(cè)Fas的缺失可成為決定哪些病人更加需要進(jìn)一步治療方案的參考因素之一。5.Fas L在膀胱尿路上皮癌中的陽(yáng)性表達(dá)率低于在良性病變,提示其膀胱腫瘤在由良性病變轉(zhuǎn)變?yōu)閻盒圆∽冃纬蛇^(guò)程中扮演著重要的作用,并在膀胱腫瘤已形成惡變形成后,不隨細(xì)胞分化程度、生長(zhǎng)情況而改變。但Fas L在正常組織中的陽(yáng)性表達(dá)高于癌組織,則需要進(jìn)一步研究。6.ING4與P53、Ki-67呈正相關(guān),與Fas/Fas L呈負(fù)相關(guān),提示膀胱腫瘤的發(fā)生和進(jìn)展是由多種因素、多個(gè)基因共同參與的一個(gè)較為復(fù)雜的演變過(guò)程,聯(lián)合檢測(cè)多個(gè)生物學(xué)指標(biāo)可能對(duì)膀胱癌的標(biāo)記物、早期診斷、精準(zhǔn)治療、術(shù)后隨訪及預(yù)后判斷提供一定的幫助。
[Abstract]:Objective: To investigate the role and clinical significance of ING4, P53, Ki-67, Fas/Fas L in the development of bladder urothelial carcinoma by detecting the expression of ING4, P53, Ki-67, Fas/Fas L in bladder urothelial carcinoma, and to analyze the relationship between ING4, P53, Ki-67, Fas/Fas L, and the markers, gene therapy, early diagnosis of bladder cancer. Methods: From 2014 to 2015, 60 specimens of bladder urothelial carcinoma, 60 adjacent tissues and 37 normal bladder mucosa were collected from the Affiliated Hospital of North Sichuan Medical College and Nanchong Central Hospital with complete clinical data. The expression of ING4, P53, Ki-67, Fas and Fas L in bladder urothelial carcinoma, adjacent tissues and normal bladder mucosa were detected. Results: 1. The positive expression rate of ING4 in bladder urothelial carcinoma was 70% (42/60), 100% (60/60) in adjacent tissues, 97.2% (36/37) in normal bladder mucosa, and 97.2% (36/37) in bladder urothelial carcinoma. The positive expression rate of ING4 in bladder urothelial carcinoma was significantly lower than that in normal bladder mucosa and adjacent tissues (P 0.05). There was no significant difference between normal bladder mucosa and adjacent tissues (P 0.05). The positive expression rate of P53 in bladder urothelial carcinoma was 96.7% (58/60), 13.3% (8/60) in paracancerous tissue, 13.5% (5/37) in normal bladder mucosa, and higher than that in normal bladder mucosa and paracancerous tissue (P 0.05). The positive expression rate of P53 in bladder urothelial carcinoma was higher than that in single bladder urothelial carcinoma (P 0.05). 3. Ki-67 in bladder urothelial carcinoma (P 0.05). The positive expression rate of urothelial carcinoma was 91.7% (55/60), 11.7% (7/60) in paracancerous tissues, 2.7% (1/37) in normal bladder mucosa, higher than that in normal bladder mucosa and paracancerous tissues (P 0.05). There was no significant difference (P 0.05). The expression of Ki-67 in bladder urothelial carcinoma increased with pathological grade or clinical stage (P 0.05). The positive expression rate of Ki-67 in multiple bladder urothelial carcinoma was higher than that in single bladder urothelial carcinoma (P 0.05). 4. Fas expression in bladder urothelial carcinoma was higher than that in single bladder urothelial carcinoma (P 0.05). The positive rate was 70% (42/60), 88.3% (53/60) in the adjacent tissues, 89.2% (34/37) in the normal bladder mucosa, and higher in the normal bladder mucosa and adjacent tissues than in the bladder urothelial carcinoma (P 0.05). The positive expression rate of Fas L in bladder urothelial carcinoma was 76.7% (46/60), 100% (60/60) in adjacent tissues, 94.6% (35/37) in normal bladder mucosa and 94.6% (35/37) in bladder urothelial carcinoma. There was no significant difference between normal bladder mucosa and adjacent tissues (P 0.05). 6. Spearman grade correlation analysis was used to analyze the relationship between ING4 and P53, Ki-67, Fas/Fas L. ING4 was negatively correlated with P53, Ki-67, and ING4 was positively correlated with Fas/Fas L. Conclusion: 1. The low expression or deletion of ING4 in bladder urothelial carcinoma suggests that ING4 may play an inhibitory role in bladder urothelial carcinoma. The high expression of P53 protein in bladder urothelial carcinoma is one of the relatively reliable clinical indicators. 2. The high expression of P53 protein in bladder urothelial carcinoma increases with the clinical stage or pathological grade of bladder cancer and the increase of the number of tumors, suggesting that the overexpression of P53 protein is one of the markers of high malignancy of bladder cancer. 3. The high expression of Ki-67 in bladder urothelial carcinoma and with the increase of bladder cancer. The clinical stage or pathological grade of urothelial carcinoma and the increasing number of tumors showed an upward trend, suggesting that Ki-67 may be one of the good indicators for the occurrence, development, diagnosis and prognosis of bladder cancer, and has important clinical significance for predicting the early recurrence, deterioration and treatment effect of bladder cancer. 4. Fas in the low surface of bladder urothelial carcinoma. It is suggested that Fas-mediated apoptotic pathway can be resisted by bladder tumor and thus has an important impact on tumor progression. Therefore, the detection of Fas-deleted may be one of the reference factors in deciding which patients need further treatment. 5. The positive expression of Fas-L in bladder urothelial carcinoma is lower than that in benign lesions, suggesting that Fas-mediated apoptotic pathway may play an important role in bladder cancer progression. Bladder tumors play an important role in the process of transformation from benign to malignant lesions, and after malignant transformation of bladder tumors, they do not change with the degree of cell differentiation and growth. S/Fas L is negatively correlated, suggesting that the occurrence and progression of bladder cancer is a complicated evolutionary process involving multiple factors and genes. Combined detection of multiple biological markers may be helpful for markers, early diagnosis, accurate treatment, postoperative follow-up and prognosis judgment of bladder cancer.
【學(xué)位授予單位】：川北醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R737.14

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本文編號(hào)：2208739