發(fā)布時間：2018-03-03 20:00

  本文選題：結直腸癌　切入點：組織因子　出處：《江蘇大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的:我們課題組前期研究闡明了體外結直腸癌(colorectal cancer,CRC)細胞株SW620表面:組織因子(tissue factor,TF)與VIIa形成復合物,直接與PAR-2(protease activated receptors-2,蛋白激酶活化受體-2)交叉對話,并促進細胞的增殖遷移[1,2];同時我們發(fā)現(xiàn)體外CRC細胞株SW620表面TF/VIIa/PAR-2軸的激活,通過激活ERK1/2與NF-κB、鈣信號等信號轉(zhuǎn)導通路及其關鍵分子,促進CRC細胞的遷移侵襲和增殖,從而促進CRC的發(fā)生發(fā)展[3-4]。新近的研究發(fā)現(xiàn),慢性炎癥促進了惡性腫瘤的發(fā)生發(fā)展。促炎細胞因子在炎癥相關腫瘤的起始、進展、和惡性轉(zhuǎn)移中扮演著關鍵角色[5]。白介素-23(Interleukin-23,IL-23)作為一種促炎細胞因子,與IL-23受體結合后,可通過NF-κB、p38 MAPK、PI3K等信號通路參與多種自身免疫性疾病的發(fā)生、發(fā)展[6-9]。我們課題組的另一項前期研究發(fā)現(xiàn),IL-23表達水平在胃癌前病變和胃癌中呈逐漸上升趨勢,有望成為胃癌早期診斷的標志物;并且,IL-23是通過活化PI3K/Akt通路促進胃癌BGC-823、SGC-7901細胞的遷移能力[10],顯示了IL-23在慢性胃炎-胃癌腫瘤進展過程中的作用。因此我們擬觀察TF、PAR-2、以及IL-23在CRC中的表達,初步探討它們和CRC的關系,為結直腸癌的診治提供新思路。材料和方法:選取2015年6月-2016年8月在江蘇大學附屬醫(yī)院普外科住院手術切除并經(jīng)病理證實的CRC的組織及相應癌旁組織標本各60份,作為實驗組和實驗對照組:免疫組化Envision法檢測組織標本中TF、PAR-2、IL-23的蛋白表達;收集患者的一般情況以及臨床病理參數(shù),卡方檢驗或者Fisher精確概率法檢驗分析三者表達與各臨床病理學參數(shù)之間的相關性。結果:1.TF、PAR-2、IL-23在CRC中的表達以及與臨床病理參數(shù)的相關性TF、PAR-2、IL-23三者均在CRC中呈高表達,與其相應的鄰近癌旁組織相比,有顯著性差異(分別為p0.0001,p0.01,p0.0001);但是TF、PAR-2、IL-23三者的表達與年齡、性別、腫瘤大小、分化程度、病理類型等均無相關性(p0.05);與較晚期的CRC的TNM分期相關(有統(tǒng)計學意義)、與淋巴結轉(zhuǎn)移相關(沒有統(tǒng)計學意義):TF的表達陽性率III/IV期顯著高于I/II期(分別為66.67%、29.63%,p0.05);有淋巴結轉(zhuǎn)移的CRC組織中TF的表達陽性率高于無淋巴結轉(zhuǎn)移的CRC組織,但是差異無統(tǒng)計學意義(分別為54.55%、40.74%,p0.05);PAR-2在III/IV期的表達顯著高于I/II期(分別為69.70%、33.33%,p0.05);在有淋巴結轉(zhuǎn)移的CRC組織中,PAR-2的表達陽性率高于無淋巴結轉(zhuǎn)移的CRC組,但是差異無統(tǒng)計學意義(分別為57.58%,44.44%,p0.05);IL-23在III/IV期的表達陽性率顯著高于I/II期(分別為66.67%、40.74%,p0.05);有淋巴結轉(zhuǎn)移的CRC組織中IL-23的表達陽性率高于無淋巴結轉(zhuǎn)移的CRC組,但是兩組差異無統(tǒng)計學意義(分別為60.61%,48.15%,p0.05)。2.TF、PAR-2、IL-23同時表達與CRC的TNM分期以及淋巴結轉(zhuǎn)移的相關性CRC組織中TF、PAR-2、IL-23均為陽性表達的比率在I/II期為37.5%,在III/IV期為83.33%,III/IV期組高于I/II期組,差異具有統(tǒng)計學意義(p0.05);在有淋巴結轉(zhuǎn)移的CRC組織中TF、PAR-2、IL-23表達均為陽性的比率為60%,在無淋巴結轉(zhuǎn)移的CRC組織中TF、PAR-2、IL-23表達均為陽性的比率為38.46%,淋巴結轉(zhuǎn)移組高于無淋巴結轉(zhuǎn)移組,但是差異無統(tǒng)計學意義(p0.05)。結論:1.TF、PAR-2、IL-23在CRC組織組中的表達顯著高于其相應的癌旁組織,并且與較晚的CRC的TNM分期有關。2.TF、PAR-2、IL-23三者在CRC中同時表達的陽性率,與較晚的TNM分期有關。3.促炎細胞因子白介素-23,與TF、PAR-2一起,均參與了CRC的發(fā)生發(fā)展,但是聯(lián)合檢測三者是否有助于CRC的診斷和預后的判斷,還需要進一步的研究證實。
[Abstract]:Objective: our previous study demonstrates in vitro colorectal cancer (colorectal cancer, CRC) SW620 cell surface: tissue factor (tissue factor, TF) to form complexes with VIIa and PAR-2 (protease activated, direct receptors-2, protein kinase activation receptor -2) and cross talk, promote cell proliferation and migration of [1,2]; at the same time we our results show that activation of CRC cells in vitro SW620 surface TF/VIIa/PAR-2 axis, through the activation of ERK1/2 and NF- K B, calcium signal signal transduction pathways and key molecules that promote the migration and proliferation of CRC cells, found in recent studies from the occurrence and development of [3-4]. and promote CRC, chronic inflammation and promote the occurrence and development of malignant tumors. The initial progress and proinflammatory cytokines in inflammatory and malignant tumors, [5]. plays a key role in the transfer of interleukin -23 (Interleukin-23, IL-23) as a proinflammatory cytokine, and IL-23 Receptor binding by NF-, p38 MAPK, K B, PI3K and other signaling pathways in various autoimmune diseases, the development of [6-9]. in our group another preliminary study found that the expression level of IL-23 increased gradually in precancerous lesions and gastric cancer, may be a marker of the early diagnosis of gastric cancer; and IL-23, through activation of the PI3K/Akt pathway to promote gastric cancer BGC-823, SGC-7901 cell migration ability of [10], shows the role of IL-23 in the progression of chronic gastritis and gastric cancer in the process. So we observe the TF, PAR-2, and the expression of IL-23 in CRC, to investigate the relationship between them and CRC, to provide new ideas for the diagnosis and treatment of colorectal cancer. Materials and methods: from June 2015 August -2016 in the Department of general surgery of Affiliated Hospital of Jiangsu University inpatient surgery and confirmed by pathology of CRC tissues and corresponding adjacent tissue specimens were collected from 60 experiments, as The experimental group and control group were detected by immunohistochemical Envision method in tissue samples of TF, PAR-2, IL-23 protein expression; general conditions were collected and the clinical pathological parameters, chi square analysis or Fisher exact test expression correlation between parameters and the clinical pathology of three. Results: 1.TF, PAR-2, TF and the correlation between the expression of IL-23 in CRC and PAR-2 with clinicopathological parameters, high expression of IL-23 were three in CRC were compared with their corresponding adjacent noncancerous tissues, there were significant differences (P0.0001, P0.01, P0.0001); but TF, PAR-2, IL-23 expression and age, gender of the three, tumor size, degree of differentiation, pathological types were not correlated (P0.05); and more advanced CRC TNM stage (statistically significant), and lymph node metastasis (not statistically significant): the expression of TF III/IV was significantly higher than that of I/II (phase respectively. 66.67%, 29.63%, P0.05); a positive expression rate of lymph node metastasis in CRC TF was higher than that without lymph node metastasis of CRC, but the difference was not statistically significant (54.55% vs 40.74%, P0.05); the expression of III/IV in PAR-2 was significantly higher than that of I/II (69.70%, 33.33%, P0.05); in lymph node metastasis in CRC tissues, the positive expression rate of PAR-2 was higher than that of CRC group without lymph node metastasis, but the difference was not statistically significant (57.58% vs 44.44%, P0.05); IL-23 in the positive expression rate of III/IV phase was significantly higher than that of I/II stage (66.67%, 40.74%, P0.05); positive the expression rate of lymph node metastasis in IL-23 CRC tissues was higher than that of non CRC group lymph node metastasis, but no significant difference between two groups (respectively 60.61%, 48.15%, P0.05).2.TF, PAR-2, IL-23 and CRC expression and TNM staging and CRC correlation between lymph node metastasis in TF, PAR-2, I L-23 is the ratio of positive expression in I/II was 37.5%, III/IV was 83.33%, III/IV group was higher than that of I/II group, the difference was statistically significant (P0.05); PAR-2 in lymph node metastasis tissues of CRC, TF, IL-23 expression was positive in the ratio of 60%, without lymph node metastasis CRC in TF, PAR-2, IL-23 expression was positive in the ratio of 38.46%, lymph node metastasis was higher than that without lymph node metastasis, but the difference was not statistically significant (P0.05). Conclusion: 1.TF, PAR-2, IL-23 expression in CRC group was significantly higher than that of the corresponding adjacent tissues, and later CRC.2.TF PAR-2, TNM staging, the positive rate of the expression of IL-23 three in CRC, and later TNM stage.3. proinflammatory cytokine interleukin -23, and TF, PAR-2, were involved in the occurrence and development of CRC, but the three combined detection is helpful to CRC diagnosis and prognosis the Further research is also needed to determine.

【學位授予單位】：江蘇大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R735.34

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