TF、PAR-2、IL-23在结直肠癌中的表达及意义

发布时间：2018-03-03 20:00

本文选题：结直肠癌　切入点：组织因子　出处：《江苏大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:我们课题组前期研究阐明了体外结直肠癌(colorectal cancer,CRC)细胞株SW620表面:组织因子(tissue factor,TF)与VIIa形成复合物,直接与PAR-2(protease activated receptors-2,蛋白激酶活化受体-2)交叉对话,并促进细胞的增殖迁移[1,2];同时我们发现体外CRC细胞株SW620表面TF/VIIa/PAR-2轴的激活,通过激活ERK1/2与NF-κB、钙信号等信号转导通路及其关键分子,促进CRC细胞的迁移侵袭和增殖,从而促进CRC的发生发展[3-4]。新近的研究发现,慢性炎症促进了恶性肿瘤的发生发展。促炎细胞因子在炎症相关肿瘤的起始、进展、和恶性转移中扮演着关键角色[5]。白介素-23(Interleukin-23,IL-23)作为一种促炎细胞因子,与IL-23受体结合后,可通过NF-κB、p38 MAPK、PI3K等信号通路参与多种自身免疫性疾病的发生、发展[6-9]。我们课题组的另一项前期研究发现,IL-23表达水平在胃癌前病变和胃癌中呈逐渐上升趋势,有望成为胃癌早期诊断的标志物;并且,IL-23是通过活化PI3K/Akt通路促进胃癌BGC-823、SGC-7901细胞的迁移能力[10],显示了IL-23在慢性胃炎-胃癌肿瘤进展过程中的作用。因此我们拟观察TF、PAR-2、以及IL-23在CRC中的表达,初步探讨它们和CRC的关系,为结直肠癌的诊治提供新思路。材料和方法:选取2015年6月-2016年8月在江苏大学附属医院普外科住院手术切除并经病理证实的CRC的组织及相应癌旁组织标本各60份,作为实验组和实验对照组:免疫组化Envision法检测组织标本中TF、PAR-2、IL-23的蛋白表达;收集患者的一般情况以及临床病理参数,卡方检验或者Fisher精确概率法检验分析三者表达与各临床病理学参数之间的相关性。结果:1.TF、PAR-2、IL-23在CRC中的表达以及与临床病理参数的相关性TF、PAR-2、IL-23三者均在CRC中呈高表达,与其相应的邻近癌旁组织相比,有显著性差异(分别为p0.0001,p0.01,p0.0001);但是TF、PAR-2、IL-23三者的表达与年龄、性别、肿瘤大小、分化程度、病理类型等均无相关性(p0.05);与较晚期的CRC的TNM分期相关(有统计学意义)、与淋巴结转移相关(没有统计学意义):TF的表达阳性率III/IV期显著高于I/II期(分别为66.67%、29.63%,p0.05);有淋巴结转移的CRC组织中TF的表达阳性率高于无淋巴结转移的CRC组织,但是差异无统计学意义(分别为54.55%、40.74%,p0.05);PAR-2在III/IV期的表达显著高于I/II期(分别为69.70%、33.33%,p0.05);在有淋巴结转移的CRC组织中,PAR-2的表达阳性率高于无淋巴结转移的CRC组,但是差异无统计学意义(分别为57.58%,44.44%,p0.05);IL-23在III/IV期的表达阳性率显著高于I/II期(分别为66.67%、40.74%,p0.05);有淋巴结转移的CRC组织中IL-23的表达阳性率高于无淋巴结转移的CRC组,但是两组差异无统计学意义(分别为60.61%,48.15%,p0.05)。2.TF、PAR-2、IL-23同时表达与CRC的TNM分期以及淋巴结转移的相关性CRC组织中TF、PAR-2、IL-23均为阳性表达的比率在I/II期为37.5%,在III/IV期为83.33%,III/IV期组高于I/II期组,差异具有统计学意义(p0.05);在有淋巴结转移的CRC组织中TF、PAR-2、IL-23表达均为阳性的比率为60%,在无淋巴结转移的CRC组织中TF、PAR-2、IL-23表达均为阳性的比率为38.46%,淋巴结转移组高于无淋巴结转移组,但是差异无统计学意义(p0.05)。结论:1.TF、PAR-2、IL-23在CRC组织组中的表达显著高于其相应的癌旁组织,并且与较晚的CRC的TNM分期有关。2.TF、PAR-2、IL-23三者在CRC中同时表达的阳性率,与较晚的TNM分期有关。3.促炎细胞因子白介素-23,与TF、PAR-2一起,均参与了CRC的发生发展,但是联合检测三者是否有助于CRC的诊断和预后的判断,还需要进一步的研究证实。
[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.

【学位授予单位】：江苏大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.34

【参考文献】