本文選題：結(jié)直腸癌 + TMEM16A�。� 參考：《大連醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:探討TMEM16A蛋白在結(jié)直腸癌組織中的表達(dá)情況與結(jié)直腸癌患者預(yù)后之間的關(guān)系,從而為結(jié)直腸癌患者的臨床治療提供新的思路和方法,同時(shí)為評(píng)估結(jié)直腸癌患者的預(yù)后提供新的檢測(cè)指標(biāo)。方法:1.搜集大連醫(yī)科大學(xué)附屬第一醫(yī)院2009年6月-2011年12月經(jīng)病理證實(shí)并得到隨訪的結(jié)直腸癌患者的術(shù)后癌組織蠟塊96例,所有患者術(shù)前均未進(jìn)行放化療和其它相應(yīng)的抗腫瘤治療,亦不伴有其他惡性腫瘤,包括:男性58例,女性38例,年齡30歲-80歲,中位年齡62.2歲;高、中、低分化分別為13例、61例、22例;無(wú)淋巴結(jié)轉(zhuǎn)移者63例,伴淋巴結(jié)轉(zhuǎn)移者33例。DukesA期6例,DukesB期57例,DukesC期33例。術(shù)后放化療者54例,無(wú)放化療者42例,所有患者的病例資料完整。生存時(shí)間記錄方法:手術(shù)日-死亡日或手術(shù)日-最后一次隨訪日期。2.用免疫組織化學(xué)SP法檢測(cè)TMEM16A蛋白在結(jié)直腸癌組織中的表達(dá)情況,分為高表達(dá)組和低表達(dá)組。3.回顧性分析患者的臨床病例資料,分析TMEM16A蛋白表達(dá)的水平與不同的臨床分期、病理特征及臨床預(yù)后的相關(guān)性。分別繪制出TMEM16A蛋白高表達(dá)組和低表達(dá)組的Kaplan-Meier生存曲線,用Log-rank檢驗(yàn)來(lái)比較兩組間的生存時(shí)間差異。單因素回歸分析結(jié)直腸癌患者術(shù)后不良預(yù)后的相關(guān)因素,多因素回歸分析TMEM16A蛋白的高表達(dá)是否為結(jié)直腸癌患者不良預(yù)后的獨(dú)立因子。結(jié)果:1、免疫組化法檢測(cè)結(jié)直腸癌組織中TMEM16A蛋白的表達(dá)情況96例結(jié)直腸癌中TMEM16A蛋白高表達(dá)組44例(45.8%),低表達(dá)組52例(54.2%)。2、結(jié)直腸癌組織中TMEM16A蛋白的表達(dá)與患者各臨床病理參數(shù)之間的關(guān)系結(jié)直腸癌組織中TMEM16A蛋白的表達(dá)程度與患者的性別、年齡、腫瘤大小及腫瘤分化的程度無(wú)相關(guān)性(P0.05),而與腫瘤的浸潤(rùn)深度、淋巴結(jié)轉(zhuǎn)移情況及臨床Dukes分期有顯著的相關(guān)性(P0.05);浸潤(rùn)≤T2組TMEM16A蛋白的高表達(dá)率為0.00%,而浸潤(rùn)T2組TMEM16A蛋白的高表達(dá)率為48.89%,兩組間的表達(dá)差異有統(tǒng)計(jì)學(xué)意義(X~2=5.415,P=0.02);臨床分期的分組中,Dukes A+B期的TMEM16A蛋白的高表達(dá)率為34.92%,Dukes C期的TMEM16A的高表達(dá)率為66.67%,兩組間的表達(dá)差異有統(tǒng)計(jì)學(xué)意義(X~2=8.791,P=0.003);淋巴結(jié)轉(zhuǎn)移組TMEM16A高表達(dá)率為66.672%,無(wú)淋巴結(jié)轉(zhuǎn)移組的陽(yáng)性表達(dá)率為34.92%,兩組間的表達(dá)差異有統(tǒng)計(jì)學(xué)意義(X~2=8.791,P=0.003)。3、結(jié)直腸癌中TMEM16A蛋白的表達(dá)與患者預(yù)后的相關(guān)性分析Kaplan-Meier生存曲線和Log-rank檢驗(yàn)的結(jié)果顯示,TMEM16A蛋白高表達(dá)組患者的5年生存率明顯低于TMEM16A蛋白低表達(dá)組(68.2%vs.92.3%),差異有統(tǒng)計(jì)學(xué)意義(Log-rank,X~2=9.892,P=0.002)。COX單因素分析結(jié)果發(fā)現(xiàn),結(jié)直腸癌患者的預(yù)后與性別(P=0.767)、腫瘤大小(P=0.084)、腫瘤的分化程度(P=0.557)、腫瘤浸潤(rùn)深度(P=0.827)無(wú)相關(guān)性,但與患者的年齡(RR=5.671,95%CI:1.303-24.678,P0.05)、有無(wú)淋巴結(jié)轉(zhuǎn)移(RR=3.645,95%CI:1.411-9.415,P0.05)、腫瘤 Dukes 分期(RR=3.645,95%CI:1.411-9.415,P0.05)、TMEM16A 蛋白的表達(dá)(RR=4.972,95%CI:1.635-15.120,P0.05)相關(guān)。COX多因素分析回歸結(jié)果顯示,校正患者性別、年齡、腫瘤的分化程度、腫瘤臨床分期及淋巴結(jié)轉(zhuǎn)移等影響因素之后,TMEM16A蛋白的高表達(dá)(P0.05,RR=6.467,95%CI:1.777-23.538)是判斷結(jié)直腸癌患者不良預(yù)后的獨(dú)立預(yù)后因子。結(jié)論:1.TMEM16A蛋白的表達(dá)水平與結(jié)直腸癌的浸潤(rùn)、Dukes分期、淋巴結(jié)轉(zhuǎn)移密切相關(guān)。2.TMEM16A蛋白的高表達(dá)是結(jié)直腸癌患者獨(dú)立的不良預(yù)后因子。3.年齡、Dukes分期、淋巴結(jié)轉(zhuǎn)移、TMEM16A蛋白的表達(dá)水平以及術(shù)后有無(wú)放化療都影響結(jié)直腸癌患者的術(shù)后預(yù)后。
[Abstract]:Objective: To investigate the relationship between the expression of TMEM16A protein in colorectal cancer and the prognosis of colorectal cancer patients, so as to provide new ideas and methods for the clinical treatment of colorectal cancer patients, and to provide new detection indicators for evaluating the prognosis of colorectal cancer patients. 1. collect the First Affiliated Hospital of Dalian Medical University, 200 9 years' June -2011 12 menstrual pathology confirmed and followed up with colorectal cancer tissue wax blocks in 96 cases of colorectal cancer patients. All patients did not undergo radiotherapy and chemotherapy and other corresponding antitumor treatment before operation, and no other malignant tumors, including 58 men, 38 women, 30 years old and 62.2 years of age; high, middle, and low differentiation, respectively. 13 cases, 61 cases, 22 cases, 63 cases with lymph node metastasis, 33 cases of.DukesA phase with lymph node metastasis, 57 cases in DukesB stage, 33 cases in DukesC stage. 54 cases were treated with radiotherapy and chemotherapy after operation, 42 cases without radiotherapy and chemotherapy. The survival time records methods: operation day death day, operation day and last follow-up date.2. use immune tissue. The expression of TMEM16A protein in colorectal cancer tissues was detected by chemical SP, and the clinical data of patients with high expression group and low expression group.3. were analyzed retrospectively. The correlation between the level of TMEM16A protein expression and different clinical stages, pathological features and clinical prognosis were analyzed. The high expression group and low table of TMEM16A protein were respectively drawn. The Kaplan-Meier survival curve of the group was compared with the Log-rank test to compare the differences in the survival time between the two groups. Single factor regression analysis was used to analyze the factors associated with the postoperative adverse prognosis of colorectal cancer patients. Multiple regression analysis of the high expression of TMEM16A protein was an independent factor for the poor prognosis of colorectal cancer patients. Results: 1, immunohistochemical method detection junction The expression of TMEM16A protein in rectal cancer tissue 96 cases of high expression of TMEM16A protein (45.8%) in colorectal cancer, 52 cases (54.2%) of low expression group (54.2%).2, the relationship between the expression of TMEM16A protein in colorectal cancer tissue and the clinicopathological parameters of the patients, the expression of TMEM16A protein in colorectal cancer tissues and the sex, age, and swelling of the patients There was no correlation between the size of tumor and the degree of tumor differentiation (P0.05), but there was a significant correlation with the depth of tumor invasion, lymph node metastasis and clinical Dukes staging (P0.05), and the high expression rate of TMEM16A protein in the group of infiltrating T2 was 0%, while the high rate of expression of TMEM16A protein in the infiltrating T2 group was 48.89%, and the difference in the expression of the two groups was statistically significant (X~). 2=5.415, P=0.02); in the group of clinical stages, the high expression rate of TMEM16A protein in Dukes A+B stage was 34.92%, the high expression rate of TMEM16A in Dukes C phase was 66.67%. The difference of expression between two groups was statistically significant (X~2=8.791, P=0.003), the TMEM16A high expression rate of lymph node metastasis group was 66.672%, and the positive expression rate of no lymph node metastasis group was 34.92%, The expression difference between the two groups was statistically significant (X~2=8.791, P=0.003).3, the correlation between the expression of TMEM16A protein in colorectal cancer and the prognosis of patients, the results of Kaplan-Meier survival curve and Log-rank test showed that the 5 year survival rate of the patients with high expression of TMEM16A protein was significantly lower than that of the low expression group of TMEM16A protein (68.2%vs.92.3%). A statistically significant (Log-rank, X~2=9.892, P=0.002).COX single factor analysis found that the prognosis of colorectal cancer patients was not related to sex (P=0.767), tumor size (P=0.084), the degree of tumor differentiation (P=0.557), and the depth of tumor invasion (P=0.827), but with the patient's age (RR=5.671,95%CI:1.303-24.678, P0.05), there was no lymph node metastasis (RR=) 3.645,95%CI:1.411-9.415, P0.05), tumor Dukes staging (RR=3.645,95%CI:1.411-9.415, P0.05), TMEM16A protein expression (RR=4.972,95%CI:1.635-15.120, P0.05) related.COX multivariate analysis of regression results showed that the correction of patient sex, age, tumor differentiation, tumor clinical stage and lymph node metastasis, and other factors, TMEM16, TMEM16. The high expression of A protein (P0.05, RR=6.467,95%CI:1.777-23.538) is an independent prognostic factor for the poor prognosis of colorectal cancer patients. Conclusion: the expression level of 1.TMEM16A protein and the invasion of colorectal cancer, Dukes staging, and lymph node metastasis closely related to the high expression of.2.TMEM16A protein are independent prognostic factors of colorectal cancer patients.3. years. Age, Dukes stage, lymph node metastasis, TMEM16A protein expression, and postoperative radiotherapy and chemotherapy all affect the prognosis of patients with colorectal cancer.

【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R735.34

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