黏蛋白1在食管鱗癌中的表達(dá)及其與臨床病理及預(yù)后的關(guān)系
發(fā)布時(shí)間:2018-01-22 06:15
本文關(guān)鍵詞: 食管鱗癌 MUC1 臨床病理 預(yù)后 出處:《山東大學(xué)》2015年碩士論文 論文類(lèi)型:學(xué)位論文
【摘要】:[背景與目的]食管癌的病理類(lèi)型中鱗癌占90%以上且患者預(yù)后不佳。目前TNM分期是判斷食管鱗癌患者預(yù)后的主要方法,但仍缺乏敏感性。故尋找準(zhǔn)確的腫瘤分子生物學(xué)標(biāo)志物判斷食管鱗癌患者的預(yù)后對(duì)于指導(dǎo)臨床治療具有重要意義。多項(xiàng)研究發(fā)現(xiàn)黏蛋白1(MUC1)在多種腫瘤細(xì)胞中高表達(dá),并與腫瘤的發(fā)生、發(fā)展、侵襲、轉(zhuǎn)移、預(yù)后等密切相關(guān)。本研究通過(guò)檢測(cè)MUC1在食管鱗癌和正常食管組織中的表達(dá),分析其表達(dá)程度與臨床病理及患者預(yù)后的關(guān)系。[方法]對(duì)2007年1月至2010年1月間接受手術(shù)治療且臨床病理資料完整的76例食管鱗癌患者進(jìn)行回顧性研究。分別采用蛋白質(zhì)免疫印跡法(Western-blotting)和免疫組織化學(xué)染色法(IHC)檢測(cè)76例食管鱗癌組織和19例正常食管粘膜組織中MUC1的表達(dá)差異,并依據(jù)文獻(xiàn)上的方法進(jìn)行結(jié)果判定。應(yīng)用SPSS19.0統(tǒng)計(jì)軟件分析,建立數(shù)據(jù)庫(kù)。采用X2檢驗(yàn)判斷相關(guān)性,采用Kaplan-Meier法進(jìn)行生存分析,采用Log-rank檢驗(yàn)判斷生存差異性,采用Cox比例風(fēng)險(xiǎn)模型進(jìn)行多因素分析判定獨(dú)立預(yù)后因素。[結(jié)果]1、Western-blotting檢測(cè):MUCl在食管鱗癌組織及正常食管組織中的相對(duì)表達(dá)水平分別為0.77±0.11和0.24±0.89,差異明顯,具有統(tǒng)計(jì)學(xué)意義(F=7.6,P0.05)。2、免疫組化檢測(cè):在食管鱗癌組織中MUC1的表達(dá)較正常食管組織中明顯升高。MUC1在正常食管組織中僅在細(xì)胞膜及部分細(xì)胞核微弱表達(dá),而在食管鱗癌組織中MUC1以細(xì)胞核表達(dá)為主,部分表達(dá)于細(xì)胞膜,這與MUC1作為一種跨膜糖蛋白在正常組織中的定位不完全相同。3、臨床病理資料的統(tǒng)計(jì)學(xué)分析和獨(dú)立預(yù)后不良因素判定:MUC1蛋白在食管鱗癌組織中的陽(yáng)性表達(dá)率為72.4%(55/76),在正常食管組織中的陽(yáng)性表達(dá)率為10.5%(2/19),兩者差異有統(tǒng)計(jì)學(xué)意義(P0.01);在T1、T2、T3+T4組中MUC1陽(yáng)性表達(dá)率分別為42.9%(6/14)、71.4%(15/21)和82.9%(34/41),差異明顯(P0.05)。腫瘤中高分化組與低分化組MUC1的陽(yáng)性表達(dá)率分別為60.0%(21/35)和82.9%(34/41),兩者差異有統(tǒng)計(jì)學(xué)意義(P0.05);有、無(wú)淋巴結(jié)轉(zhuǎn)移者的MUC1陽(yáng)性表達(dá)率分別為86.1%(31/36)和60.0%(24/40),兩者差異明顯(P0.01),而MUC1的表達(dá)與患者的性別、年齡、病變長(zhǎng)度及TNM分期無(wú)明顯相關(guān)(P0.05);颊呖傮w5年生存率為25.0%(19/76),伴有MUC1表達(dá)陽(yáng)性患者的5年生存率為16.4%(9/55),表達(dá)陰性患者5年生存率為47.6%(10/21),差異有統(tǒng)計(jì)學(xué)意義(P0.05)。COX回歸分析顯示,淋巴結(jié)轉(zhuǎn)移(P=0.007)、T分期(P=0.043)及MUC1的陽(yáng)性表達(dá)(P=0.01)是獨(dú)立的預(yù)后不良因素。[結(jié)論]MUC1在食管鱗癌組織中的表達(dá)明顯高于其在正常食管組織中的表達(dá);MUC1在食管鱗癌組織中的表達(dá)以細(xì)胞核表達(dá)為主,隨著T分期的升高,MUC1的陽(yáng)性表達(dá)率也逐漸升高;腫瘤中-高分化組中MUC1的陽(yáng)性表達(dá)率明顯低于低分化組;MUC1在淋巴結(jié)轉(zhuǎn)移陰性組中的陽(yáng)性表達(dá)率明顯低于陽(yáng)性組,這提示腫瘤的侵襲性隨著MUC1的表達(dá)升高而不斷增強(qiáng)。伴有MUC1表達(dá)陽(yáng)性患者的5年生存率明顯低于表達(dá)陰性患者,MUC1可以作為評(píng)估患者預(yù)后的分子生物學(xué)標(biāo)志。
[Abstract]:[Objective] background and pathological types of esophageal carcinoma and squamous cell carcinoma accounted for more than 90% patients with poor prognosis. The TNM classification is the main method to determine the prognosis of patients with esophageal squamous cell carcinoma, but still lack of sensitivity. So looking for accurate markers of tumor molecular biology prognosis in patients with esophageal squamous cell carcinoma has important significance for guiding the clinical treatment of a number of studies have found. Mucin 1 (MUC1) high expression in tumor cells, and tumor occurrence, development, invasion, metastasis, prognosis and other closely related. This study through the detection of MUC1 in esophageal squamous cell carcinoma and normal esophageal tissues, relation analysis method.] the expression level and clinical pathology and prognosis of January 2007 to January 2010 underwent surgical treatment and clinical pathological data of 76 cases of esophageal squamous cell carcinoma were studied retrospectively. Using Western blot (Western-blotting) And immunohistochemical staining (IHC) expression of MUC1 was detected in 76 cases of esophageal squamous cell carcinoma and 19 cases of normal esophageal mucosa, and according to the method of literature on decision making. The establishment of database analysis, using SPSS19.0 statistical software. X2 test was used to determine the correlation, survival analysis was performed by Kaplan-Meier method, using Log-rank test to judge the difference in survival, Cox proportional hazards model was used in multivariate analysis to determine the independent prognostic factors. Results:]1, Western-blotting detection of MUCl in esophageal squamous cell carcinoma tissues and normal esophageal tissues relative expression levels were 0.77 + 0.11 and 0.24 + 0.89, significant difference was statistically significant (F=7.6, P0.05).2, immunohistochemistry detection: the expression of MUC1 in esophageal squamous cell carcinoma than in normal esophageal tissues was significantly increased.MUC1 in normal esophageal tissues only in the cell membrane and nuclear weak While the expression of MUC1 in esophageal squamous cell carcinoma with nuclear expression, some expression in the cell membrane, and the positioning of MUC1 as a transmembrane glycoprotein in normal tissues is not the same as.3, determine the statistical analysis of clinical data and independent adverse prognostic factors: the positive expression of MUC1 protein in esophageal squamous cell carcinoma rate 72.4% (55/76), the positive expression in normal esophageal tissues was 10.5% (2/19), the difference was statistically significant (P0.01); in T1, T2, T3+T4 in the group of MUC1 positive expression rate was 42.9% (6/14), 71.4% (15/21) and 82.9% (34/41), significant difference (P0.05) the positive expression of tumor in highly and poorly differentiated groups of MUC1 rates were 60% (21/35) and 82.9% (34/41), the difference was statistically significant (P0.05); the positive expression of MUC1 had no lymph node metastasis rate are 86.1% (31/36) and 60% (24/40), two Cha Yiming Display (P0.01), and the expression of MUC1 and the patients' sex, age, lesion length and TNM stage (P0.05). There was no obvious correlation with the overall 5 year survival rate was 25% (19/76), accompanied by the expression of MUC1 positive patients 5 year survival rate was 16.4% (9/55), the expression of negative patients 5 year survival rate 47.6% (10/21), the difference was statistically significant (P0.05).COX regression analysis showed that lymph node metastasis (P=0.007), T stage (P=0.043) and the positive expression of MUC1 (P=0.01) expression is independent prognostic factor. Conclusion]MUC1 in esophageal squamous cell carcinoma is significantly higher than in normal esophageal tissues; the expression of MUC1 in esophageal squamous cell carcinoma with nuclear expression, with the T staging, the positive expression rate of MUC1 also increased gradually; the positive expression of tumor in highly differentiated group of MUC1 was significantly lower than the low differentiation group; positive negative expression group of MUC1 in lymph node metastasis The rate is significantly lower than that of the positive group. This indicates that the aggressiveness of tumors increases with the increase of MUC1 expression. The 5 year survival rate of patients with MUC1 expression is significantly lower than that of patients with negative expression. MUC1 can be used as a molecular biomarker for evaluating prognosis of patients.
【學(xué)位授予單位】:山東大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2015
【分類(lèi)號(hào)】:R735.1
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 王洲,劉相燕,劉凡英,陳景寒;N_0期食管癌術(shù)后早期復(fù)發(fā)與淋巴結(jié)微轉(zhuǎn)移的相關(guān)性研究[J];中華外科雜志;2004年02期
,本文編號(hào):1453921
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