本文選題：食管胃交界腺癌　切入點(diǎn)：SPG20　出處：《河北醫(yī)科大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:食管胃交界腺癌(adenocarcinoma of esophagogastric junction,AEGJ)是發(fā)生于食管與胃交界區(qū)域內(nèi),侵及食管胃交界(齒狀線)的腺癌。手術(shù)是治療食管胃交界腺癌的主要治療方式,但術(shù)后腫瘤復(fù)發(fā)及淋巴結(jié)轉(zhuǎn)移是增加其死亡率的一項(xiàng)重要原因,其根治術(shù)后5年生存率仍不足30%,而且在近十幾年來并無顯著改善,較早出現(xiàn)淋巴結(jié)轉(zhuǎn)移、預(yù)后差是食管胃交界腺癌的重要生物學(xué)特征,但其原因及機(jī)制目前仍不清楚。既往研究證實(shí),能夠編碼Spartin蛋白的SPG 20基因的甲基化在結(jié)直腸癌中水平較高,導(dǎo)致Spartin蛋白的低表達(dá),而正常的粘膜組織Spartin蛋白表達(dá)水平較高。因此,Spartin蛋白可能成為腺癌的分子標(biāo)志物和致癌機(jī)制之一。本文旨在通過觀察Spartin蛋白在食管胃交界腺癌中的表達(dá)水平,探討其與食管為交界腺癌發(fā)生、發(fā)展之間的關(guān)系,為食管胃交界腺癌發(fā)生的機(jī)制提供新的研究方向。方法:標(biāo)本取自河北醫(yī)科大學(xué)第四醫(yī)院2013年10月-2014年02月期間行手術(shù)治療的60例食管胃交界腺癌患者,其中男40例,女20例;年齡46~72歲,平均(54.5±6.9)歲。所有標(biāo)本經(jīng)HE染色病理證實(shí)為腺癌。手術(shù)切除標(biāo)本0.5 h內(nèi)取新鮮癌組織、正常粘膜組織。福爾馬林固定,石蠟包埋,制作石蠟切片,用于免疫組織化學(xué)染色。應(yīng)用免疫組織化學(xué)SP法分別檢測(cè)60份標(biāo)本癌組織及正常粘膜組織中Spartin蛋白的表達(dá)情況。應(yīng)用彩色病理圖像分析系統(tǒng)在高倍鏡下測(cè)定免疫組化結(jié)果。所得試驗(yàn)數(shù)據(jù)通過SPSS 16.0統(tǒng)計(jì)軟件進(jìn)行處理,兩組比較采用t檢驗(yàn),計(jì)量資料采用平均數(shù)±標(biāo)準(zhǔn)差,計(jì)數(shù)資料采用χ2檢驗(yàn)比較各指標(biāo)的相互關(guān)系。P0.05表示差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:1全部60例食管胃交界腺癌組織中,其中23例Spartin蛋白表達(dá)呈陽性,陽性表達(dá)率為38.33%;食管胃交界腺癌患者正常粘膜組織組織60例,其中50例Spartin基因蛋白表達(dá)呈陽性,陽性表達(dá)率為83.33%,食管胃交界腺癌患者正常粘膜組織Spartin蛋白陽性表達(dá)率顯著高于癌組織(P0.01);2 Spartin蛋白水平隨臨床分期增高、分化程度降低及發(fā)生淋巴結(jié)轉(zhuǎn)移而明顯降低,不同分期之間比較具有顯著差異(χ2=9.212,P=0.018),不同分化程度比較有顯著性差異(χ2=12.564,P=0.011),有淋巴結(jié)轉(zhuǎn)移患者Spartin蛋白水平較低(χ2=9.414,P0.005)。Spartin蛋白水平與食管胃交界腺癌患者的性別、年齡、分化程度、腫瘤大小、組織分型及浸潤深度無關(guān)(P0.05);3全部60例食管胃交界腺癌參與術(shù)后隨訪,隨訪時(shí)間為16個(gè)月以上,觀察術(shù)后吻合口局部復(fù)發(fā)情況,縱隔、腹腔淋巴結(jié)轉(zhuǎn)移及遠(yuǎn)處轉(zhuǎn)移情況。術(shù)后16個(gè)月無進(jìn)展生存者46例,腫瘤進(jìn)展者14例,其中吻合口復(fù)發(fā)1例,縱隔、腹腔淋巴結(jié)轉(zhuǎn)移5例,遠(yuǎn)處轉(zhuǎn)移9例(1例為縱隔淋巴結(jié)及肝多發(fā)轉(zhuǎn)移);4隨訪的60例患者,23例癌組織Spartin蛋白陽性表達(dá)者術(shù)后16個(gè)月發(fā)生復(fù)發(fā)轉(zhuǎn)移4例,16個(gè)月無進(jìn)展生存率為82.61%;Spartin蛋白陰性表達(dá)者37例,觀察至術(shù)后16個(gè)月出現(xiàn)復(fù)發(fā)轉(zhuǎn)移10例,16個(gè)月無進(jìn)展生存率為72.93%;5對(duì)腫瘤大小、分化程度、浸潤深度、淋巴結(jié)轉(zhuǎn)移、臨床分期和Spartin蛋白表達(dá)等臨床病理因素采用COX多因素分析,結(jié)果表明食管胃交界腺癌患者分化程度、臨床分期、浸潤深度和Spartin蛋白表達(dá)可以作為獨(dú)立預(yù)測(cè)因子,浸潤深度增加,患者復(fù)發(fā)轉(zhuǎn)移風(fēng)險(xiǎn)增大(風(fēng)險(xiǎn)度=4.561,P=0.032),腺癌分化程度越低,患者復(fù)發(fā)轉(zhuǎn)移風(fēng)險(xiǎn)也越高(風(fēng)險(xiǎn)度=5.620,P=0.017),臨床分期的越高,患者復(fù)發(fā)轉(zhuǎn)移風(fēng)險(xiǎn)增大(風(fēng)險(xiǎn)度=5.254,P=0.021),患者出現(xiàn)淋巴結(jié)轉(zhuǎn)移,患者復(fù)發(fā)轉(zhuǎn)移風(fēng)險(xiǎn)增大(風(fēng)險(xiǎn)度=3.998,P=0.045);Spartin蛋白表達(dá)低,患者復(fù)發(fā)轉(zhuǎn)移風(fēng)險(xiǎn)增大(風(fēng)險(xiǎn)度=2.998,P=0.025)。結(jié)論:1 Spartin蛋白在食管胃交界腺癌組織中低表達(dá),與正常粘膜組織有顯著性差異,提示Spartin蛋白缺失表達(dá)可能在食管胃交界腺癌發(fā)生過程中具有重要作用,可能與食管胃交界腺癌的發(fā)生、發(fā)展有關(guān);2食管胃交界腺癌患者癌組織中Spartin蛋白表達(dá)水平與臨床分期、分化程度及是否有淋巴結(jié)轉(zhuǎn)移有關(guān);3 Spartin蛋白表達(dá)異常者具有明顯的術(shù)后復(fù)發(fā)、轉(zhuǎn)移風(fēng)險(xiǎn),提示Spartin蛋白表達(dá)可能成為食管胃交界腺癌預(yù)后預(yù)測(cè)因子。
[Abstract]:Objective: gastroesophageal junction adenocarcinoma (adenocarcinoma of esophagogastric junction, AEGJ) occurred in the esophagus and gastric junction area, at the junction of invasion of esophageal and gastric adenocarcinoma (dentate line). Surgery is the main treatment of adenocarcinoma of the esophagogastric junction, but the postoperative tumor recurrence and lymph node metastasis is a an important reason for its mortality, the radical postoperative 5 years survival rate is still less than 30%, and there is no significant improvement in the past ten years earlier, lymph node metastasis, poor prognosis is an important biological feature of gastroesophageal junction adenocarcinoma, but its causes and mechanism are still unclear. The previous studies showed that methylation can encoding Spartin SPG protein 20 gene level in colorectal cancer, leading to low expression of Spartin protein in normal gastric mucosa, and the expression level of Spartin protein is higher. Therefore, Spartin protein may be molecular for adenocarcinoma of the subject One of the markers and carcinogenic mechanism. This paper aims at the expression level of junction carcinoma in esophagus and stomach through the observation of Spartin protein, and to evaluate the esophagus junction adenocarcinoma, relationship between development, provide a new research direction for the esophagogastric junction adenocarcinoma mechanism. Methods: the samples were taken from the fourth hospital of Hebei Medical University during -2014 October 2013 in 02 months in 60 cases of surgical treatment of gastroesophageal junction adenocarcinoma patients, 40 were male, 20 were female; aged 46~72 years old, the average (54.5 + 6.9) years old. All specimens were confirmed by HE staining for adenocarcinoma. Surgical specimens within 0.5 h from the fresh cancer tissue and normal mucosa of formalin. Fixed, paraffin, paraffin sections were used for immunohistochemical staining. The expression of Spartin protein were detected in 60 specimens of carcinoma and normal mucosa tissues by SP immunohistochemical method. By pathological color Analysis system for determination of immune group at high magnification of the image. The experimental data were processed by statistical software SPSS 16, the two groups were compared with t test, measurement data with the average standard deviation, count data using 2 test comparison of each index between.P0.05 table was statistically significant difference. The results shows: the junction 1 of all the 60 patients with esophageal and gastric adenocarcinoma, including 23 cases of Spartin protein expression was positive, the positive rate was 38.33%; adenocarcinoma of the esophagogastric junction patients with normal mucosa tissue in 60 cases, including 50 cases of Spartin gene protein expression was positive, the positive rate was 83.33%, the positive expression of Spartin protein in esophageal gastric junction adenocarcinoma in patients with normal mucosa tissues was significantly higher than that in cancer tissue (P0.01); 2 Spartin protein level increased with the clinical stage, degree of differentiation and reduce the occurrence of lymph node metastasis decreased significantly with comparison between different stages. There were significant differences (2=9.212, P=0.018), different differentiation degree had significant difference (2=12.564, P=0.011), lymph node metastasis, Spartin protein levels were lower (2=9.414, P0.005).Spartin protein level and gastroesophageal junction adenocarcinoma patients with gender, age, differentiation degree, tumor size, histological the type and depth of invasion (P0.05); followed up 3 of all 60 cases of adenocarcinoma of the esophagogastric junction in the postoperative follow-up time was 16 months, and local recurrence of mediastinal anastomosis, postoperative observation, lymph node metastasis and distant metastasis of abdominal cavity. After 16 months of progression free survival in 46 cases, 14 cases the tumor progression, including anastomotic recurrence in 1 cases, mediastinal and abdominal lymph node metastasis in 5 cases, 9 cases with distant metastases (1 cases of mediastinal lymph node and liver metastasis); 60 cases of 4 follow-up patients, 23 cases of positive expression of Spartin protein in cancer patients after 16 months of recurrence and metastasis 4 cases, 16 months of progression free survival rate was 82.61%; 37 cases of Spartin negative expression, to observe 16 months after surgery, recurrence and metastasis in 10 cases, 16 month progression free survival rate was 72.93%; 5 of the tumor size, degree of differentiation, depth of invasion, lymph node metastasis, clinical stage by multivariate analysis with COX and Spartin protein expression and other clinicopathological factors. The results show that the degree of differentiation of gastroesophageal junction adenocarcinoma patients, clinical stage, the expression can be used as independent predictors of the depth of invasion and Spartin protein, infiltration depth increased, with increased risk of recurrence (hazard ratio =4.561, P=0.032), the degree of differentiation of adenocarcinoma of the lower risk of recurrence and metastasis in patients (the higher the risk of =5.620, P=0.017), the higher clinical stage, recurrence and metastasis of patients with increased risk (risk =5.254, P=0.021), patients with lymph node metastasis, recurrence and metastasis in patients with increased risk (the risk of =3.998, P=0.045, Sparti); The low expression of N protein in patients with increased risk of recurrence and metastasis (hazard ratio =2.998, P=0.025). Conclusion: the low expression of Spartin protein at the junction of 1 adenocarcinoma in esophagus and stomach, and there was significant difference compared with normal mucosa, suggesting that loss of Spartin protein expression may play an important role in the occurrence of gastroesophageal junction adenocarcinoma and esophageal process gastric junction adenocarcinoma, development; 2 esophagogastric junction cancer tissues of patients with adenocarcinoma of the expression level of Spartin protein and clinical stage, degree of differentiation and lymph node metastasis; 3 Spartin protein abnormal expression with recurrence, obvious postoperative metastasis risk, suggesting that Spartin protein expression may become esophagogastricjunction prognosis adenocarcinoma predictors.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R735

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1 李立彬;Spartin蛋白在食管胃交界腺癌中的表達(dá)及意義[D];河北醫(yī)科大學(xué);2015年

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本文編號(hào)：1592822