發(fā)布時間：2018-02-21 11:33

  本文關(guān)鍵詞： 結(jié)直腸癌 尾型同源盒轉(zhuǎn)錄因子2 環(huán)氧合酶2 預(yù)后 免疫組織化學(xué)　出處：《大連醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:在我國,近30年結(jié)直腸癌的發(fā)病率和死亡率均呈上升趨勢,而且多數(shù)患者發(fā)現(xiàn)時已屬于中晚期。近年來越來越多的研究發(fā)現(xiàn)尾型同源盒轉(zhuǎn)錄因子2(caudal-related homeobox transcription factor 2,CDX2)及環(huán)氧合酶2(cyclooxygenase2,COX2)共同參與結(jié)直腸癌的形成、侵襲、轉(zhuǎn)移過程,而且CDX2可通過多條信號轉(zhuǎn)導(dǎo)途徑調(diào)控COX2的轉(zhuǎn)錄和表達(dá),兩者之間關(guān)系密切。本實驗通過研究CDX2及COX2在結(jié)直腸癌組織中蛋白的表達(dá)情況,探討二者的表達(dá)與結(jié)直腸癌各項臨床病理因素之間的相關(guān)性,二者之間表達(dá)的相關(guān)性以及二者的表達(dá)與結(jié)直腸癌患者的預(yù)后的相關(guān)性,為結(jié)直腸癌的早期診斷和預(yù)后評估提供理論依據(jù)。方法:收集大連醫(yī)科大學(xué)附屬第一醫(yī)院2009年6月-2011年6月經(jīng)手術(shù)后病理證實的結(jié)直腸腺癌患者的術(shù)后結(jié)直腸癌組織石蠟包埋標(biāo)本44例。所有患者均行結(jié)直腸癌根治術(shù)治療,術(shù)前均未接受放療和化療,臨床及病理資料完整。術(shù)后采用電話方式進行隨訪,起點為手術(shù)之日,終點為患者出現(xiàn)死亡、失訪或至截止時間(2016年6月3日)。隨訪結(jié)束時,獲得完整隨訪資料40例,隨訪率為90.9%,15例結(jié)直腸癌患者死亡。同時選取距腫瘤大于3cm的切緣正常組織作為對照組。采用免疫組化染色法檢測44例結(jié)直腸腺癌及其對應(yīng)癌旁正常結(jié)直腸黏膜組織標(biāo)本的CDX2及COX2的蛋白表達(dá)水平。統(tǒng)計學(xué)分析:(1)運用χ2檢驗及Fisher確切概率法分析腫瘤組織CDX2及COX2的表達(dá)與臨床病理因素的關(guān)系;(2)運用Spearman秩和檢驗分析CDX2和COX2在結(jié)直腸癌中表達(dá)水平的相關(guān)性;(3)運用Kaplan-Melen法、Log-rank檢驗分析腫瘤組織CDX2及COX2的表達(dá)與患者總生存期(OS)、無病生存期(DFS)、術(shù)后生存時間、5年生存率的關(guān)系。結(jié)果:1.CDX2在結(jié)直腸癌組織與癌旁正常組織中呈現(xiàn)不同程度表達(dá),在結(jié)直腸癌組織中陽性表達(dá)為65.9%(29/44),而在癌旁正常結(jié)直腸黏膜組織中陽性表達(dá)為93.2%(41/44),兩組間差異存在統(tǒng)計學(xué)意義,χ2=10.057,P=0.003。COX2在結(jié)直腸癌組織與癌旁正常組織中呈現(xiàn)不同程度表達(dá),在結(jié)直腸癌組織中陽性表達(dá)為72.7%(32/44),而在癌旁正常結(jié)直腸黏膜組織中陽性表達(dá)為25.0%(11/44),兩組間差異存在統(tǒng)計學(xué)意義,χ2=20.056,P0.001。2.CDX2的表達(dá)水平與性別(P=0.431)、年齡(P=0.294)、TNM分期(P=0.184)、侵潤深度(P=0.135)、遠(yuǎn)處轉(zhuǎn)移(P=0.07)無顯著相關(guān)性,而與分化程度(P=0.049)、左右半結(jié)腸部位(P=0.034)、淋巴結(jié)轉(zhuǎn)移(P=0.034)、5年生存率(P=0.048)顯著相關(guān)。COX2的表達(dá)水平與性別(P=0.658)、年齡(P=0.873)、TNM分期(P=0.75)、侵潤深度(P=0.333)、遠(yuǎn)處轉(zhuǎn)移(P=0.53)、分化程度(P=0.826)、左右半結(jié)腸部位(P=0.388)、淋巴結(jié)轉(zhuǎn)移(0.622)均無顯著相關(guān)性,P值均0.05,均無統(tǒng)計學(xué)意義。3.CDX2和COX2在結(jié)直腸癌腫瘤組織中表達(dá)的相關(guān)性,用Spearman秩和檢驗相關(guān)性分析來分析發(fā)現(xiàn)兩者在結(jié)直腸癌組織中的表達(dá)呈明顯負(fù)相關(guān),且具有統(tǒng)計學(xué)意義(r=-0.339,P=0.0240.05)。4.用Kaplan-Meier方法和Log-rank檢驗進行生存分析,CDX2陰性組患者中位OS為39.86個月,明顯低于CDX2陽性組的62.09個月,χ2=6.844,P=0.009,有統(tǒng)計學(xué)意義。CDX2陰性組患者中位DFS為26.79個月,明顯低于CDX2陽性組的51.65個月,χ2=7.246,P=0.007,也具有統(tǒng)計學(xué)意義。COX2陰性組患者中位OS為55.23個月,中位DFS為44.86個月,COX2陽性組中位OS為54.70個月,中位DFS為43.02個月。生存分析兩組OS之間差異沒有統(tǒng)計學(xué)意義,χ2=0.901,P=0.342;兩組DFS之間差異同樣沒有統(tǒng)計學(xué)意義,χ2=0.940,P=0.332。5.在有淋巴結(jié)轉(zhuǎn)移的亞組中,CDX2陰性組的術(shù)后生存時間明顯短于CDX2陽性組,且差異有統(tǒng)計學(xué)意義,P=0.001;而在無淋巴結(jié)轉(zhuǎn)移的亞組中,CDX2陰性組的術(shù)后生存時間與CDX2陽性組之間差異無統(tǒng)計學(xué)意義,P=0.617。結(jié)論:1.CDX2在結(jié)直腸癌組織中的表達(dá)水平明顯低于正常結(jié)直腸組織,其表達(dá)與結(jié)直腸癌分化程度、左右半結(jié)腸部位、淋巴結(jié)轉(zhuǎn)移相關(guān),與5年生存率、OS、DFS、術(shù)后生存時間相關(guān)。其表達(dá)缺失或下調(diào)提示不良預(yù)后,尤其是對于淋巴結(jié)陽性的患者。CDX2可能成為預(yù)測結(jié)直腸癌預(yù)后的生物標(biāo)志物。2.COX2在結(jié)直腸癌組織中的表達(dá)水平明顯高于正常結(jié)直腸組織。但其表達(dá)與各項臨床病理因素及患者OS及DFS均無相關(guān)性,不能作為結(jié)直腸癌的預(yù)后指標(biāo)。3.CDX2和COX2在結(jié)直腸癌中的表達(dá)呈負(fù)相關(guān),表明CDX2在結(jié)直腸癌中的缺失可能誘導(dǎo)激活COX2的表達(dá),兩者可能均參與了結(jié)直腸癌的發(fā)生發(fā)展,為腫瘤精準(zhǔn)治療提供了新的潛在靶點。
[Abstract]:Objective: in China, nearly 30 years the incidence and mortality of colorectal cancer showed an upward trend, and most patients were found in the late fall. In recent years, more and more studies have found caudal type homeobox transcription factor 2 (caudal-related homeobox transcription factor 2, CDX2) and cyclooxygenase 2 (cyclooxygenase2, COX2) to participate in the formation of colorectal cancer, invasion, metastasis, and CDX2 transcription through multiple signal transduction pathways and the regulation of COX2 expression, the close relationship between the two. The expression of fabric in protein in colorectal cancer group through the study of CDX2 and COX2, the correlation between the expression and clinicopathological factors in colorectal cancer two the correlation between the expression of the correlation between the two and two expression in patients with colorectal carcinoma and the prognosis, and provide a theoretical basis for early diagnosis and prognosis of colorectal cancer. Methods: the First Affiliated Hospital of Dalian Medical University from June 2009 6 menstrual surgery after -2011 years of pathology in patients with colorectal adenocarcinoma after resection of colorectal cancer paraffin embedded specimens from 44 cases. All patients underwent radical resection of colorectal cancer treatment, were not receiving preoperative radiotherapy and chemotherapy, complete clinical and pathological data after surgery by telephone. Follow up, the starting point for the date of surgery, end point for patients died or lost to the deadline (June 3, 2016). At the end of the follow-up, 40 cases received complete follow-up, follow-up rate was 90.9%, 15 cases of colorectal cancer patients died. At the same time selected from a tumor more than 3cm margin normal tissues as control group. The expression of CDX2 and COX2 detected by immunohistochemical method in 44 cases of colorectal adenocarcinoma and adjacent normal colorectal mucosa tissue protein. Statistical analysis: (1) using the 2 test and Fis Analysis of the relationship between the expression of CDX2 and COX2 in tumor tissues and the clinicopathological factors of her exact probability method; (2) using the Spearman rank sum test and analysis of CDX2 and COX2 in colorectal cancer the expression level of correlation; (3) using Kaplan-Melen method, Log-rank test analysis of the expression of CDX2 and COX2 in tumor tissue and overall survival (OS), disease free survival (DFS), postoperative survival time, the relationship between the survival rate of 5 years. Results: 1.CDX2 showed different degrees in colorectal cancer tissue and adjacent normal tissue expression in colorectal cancer tissues the positive expression was 65.9% (29/44), while the positive expression in adjacent normal colorectal mucosa tissues 93.2% (41/44), statistically significant differences between the two groups of X 2=10.057, P=0.003.COX2 showed different degrees in colorectal cancer tissue and adjacent normal tissue expression in colorectal cancer tissues the positive expression was 72.7% (32/44), and in adjacent normal The positive expression in colorectal tissues was 25% (11/44), statistically significant differences between the two groups of X 2=20.056, the expression level of P0.001.2.CDX2 and gender (P=0.431), age (P=0.294), TNM stage (P=0.184), the depth of invasion (P=0.135), distant metastasis (P= 0.07) had no significant correlation with differentiation, and degree (P=0.049), left and right half colon (P=0.034), lymph node metastasis (P=0.034), the 5 year survival rate (P=0.048) expression level and gender were significantly related to.COX2 (P=0.658), age (P=0.873), TNM stage (P=0.75), the depth of invasion (P=0.333), distant metastasis (P=0.53), differentiation degree (P=0.826), left and right half colon (P=0.388), lymph node metastasis (0.622) had no significant correlation, P value was 0.05, there was no statistically significant correlation between the expression of.3.CDX2 and COX2 in colorectal carcinoma, was analyzed by Spearman rank sum test correlation analysis found both in colorectal cancer group There was a negative correlation in the expression of the fabric, and have statistical significance (r=-0.339, P=0.0240.05).4. survival was analyzed by Kaplan-Meier method and Log-rank test, the CDX2 negative patients the median OS was 39.86 months, significantly less than 62.09 months, CDX2 positive group were 2=6.844, P=0.009, was statistically significant in patients with.CDX2 negative the median DFS was 26.79 months, significantly less than 51.65 months, CDX2 positive group was 2=7.246, P=0.007 was also statistically significant in patients with.COX2 negative OS was 55.23 months, median DFS was 44.86 months in COX2 positive group, the median OS was 54.70 months, median DFS was 43.02 months the difference between the two groups. The survival analysis of OS was not statistically significant, X 2=0.901, P=0.342; the difference between the two groups was not statistically significant DFS the same, X 2=0.940, P=0.332.5. in lymph node metastasis group, CDX2 negative group the postoperative survival time was significantly shorter in the CDX2 positive group, and A statistically significant difference in P=0.001; and without lymph node metastasis subgroup, CDX2 negative group the postoperative survival time and the difference between the CDX2 positive group was not statistically significant. Conclusion: the P=0.617. expression of 1.CDX2 in colorectal cancer tissues was significantly lower than that in normal colorectal tissues, its expression and degree of differentiation of colorectal cancer, about half the colon, lymph node metastasis, and 5 year survival rate, OS, DFS, postoperative survival time. Its expression is down regulated or absent prognostic factors, especially for patients with positive lymph nodes may become.CDX2 expression level of predictive biomarkers of.2.COX2 colorectal cancer prognosis in colorectal cancer tissues was significantly higher than normal colorectal tissue. But its expression had no correlation with the clinical and pathological factors of patients with OS and DFS, the expression can not be used as colorectal cancer prognostic indicators of.3.CDX2 and COX2 in colorectal cancer A negative correlation indicates that the loss of CDX2 in colorectal cancer may induce the activation of COX2 expression. Both of them may participate in the occurrence and development of colorectal cancer, and provide new potential targets for precise treatment of tumors.

【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735.34

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