OPN与CD44在结直肠癌及其肝转移组织中的表达、临床意义与预后

发布时间：2018-09-18 19:35

【摘要】：背景与目的:结直肠癌肝转移在结直肠癌患者中十分常见,极大影响患者术后生存期,临床上难以治愈,然而目前对于肝转移的患者缺乏早期诊断的敏感肿瘤标志物,治疗上虽然手术切除能延长患者一定的生存时间,但手术切除率较低,难以完全切净病灶,治疗效果不佳,缺乏有效地靶向治疗药物。结直肠癌肝转移的发病机制十分复杂,涉及多个基因、趋化因子,细胞因子及多条细胞通路等,目前对其机制的研究尚未完全阐明,进一步研究其表达的介质,有助于揭示结直肠癌肝转移的影响因素,指导临床工作。研究证实,骨桥蛋白的mRNA以及其相应的表达的蛋白在结直肠良性肿瘤以及恶性肿瘤的组织中集聚,而在结直肠黏膜组织中呈现低表达,其参与结直肠肿瘤从良性到恶性的发生以及恶变后的周围侵袭及转移,CD44是骨桥蛋白的受体之一,其在结直肠癌原发灶中呈表达(+),且表达率较高,此外,在转移的系膜淋巴组织中的表达率也升高,而在结直肠黏膜组织中表达则相反,研究结果表明,CD44参与细胞迁移,经过激活各种信号通路增加肿瘤细胞增殖和远处转移的几率。基于以上研究成果,我们推测OPN与CD44的表达存在一定相关性,并且与肿瘤的恶性程度及分期有关,能指导患者预后及针对性治疗。研究结果有望进一步阐明OPN与CD44与临床病理的关系以及二者的相关性和对预后的指导意义,为临床治疗结直肠癌肝转移提供新的靶点及治疗方法。方法:病例采集2008年1月至2009年12月于北京军区总医院全军普通外科中心经全系膜根治性切除手术治疗的结肠癌或者直肠癌患者的组织标本76例,包括取同一患者标本的癌旁10cm处的正常黏膜组织30例,肝脏转移癌组织16例进行S-P法检测OPN与CD44在上述标本中的表达情况,随访患者的生存期,使用统计学软件SPSS19.0进行处理,OPN阳性和阴性组、CD44阳性与阴性组之间的比较用χ2检验,组间比较经统计学软件分析后P值小于0.05为差异有意义,患者术后5年生存率用Kplan-Meier曲线进行分析,比较二者表达对预后的影响。结果76例结直肠癌组织中OPN高表达的有53例(69.7%),CD44高表达的有40例(52.6%),30例癌旁正常黏膜组织中高表达OPN的有2例(6.7%),高表达CD44的有5例(16.7%),16例肝脏转移灶中OPN表达阳性的有12(75.0%)例,CD44在远处转移灶中表达阳性的有11(68.8%)例。OPN和CD44在CC的腺癌组织中及其肝脏转移组织中呈现表达升高的现象,而正常黏膜则相反,二者的差别经过统计学分析,有统计学意义(P0.001)。OPN与CD44表达阳性的患者,在肿瘤侵犯肠壁的深度增加、淋巴结转移阳性以及肝转移阳性的组织中,阳性表达率高,而肿瘤分化差的患者OPN表达率高,但是,CD44表达程度的高低与肿瘤的分化程度无关。OPN与CD44在结直肠癌原发灶特别是肝转移灶中的高表达有明显相关性。OPN和CD44在结直肠腺癌组织中表达阳性的患者术后5年生存率较OPN和CD44表达低的患者明显下降,经统计学软件分析,差异显著(P0.05)。结论在结直肠腺癌组织中,OPN与CD44免疫组化结果为高表达,在其肝脏转移组织中,二者表达率也很高,并且二者在上述两种组织中的表达率显著高于对应的正常组织中的表达,因此,二者在原发灶及转移癌组织中的表达率高与恶性肿瘤局部浸润和远处转移关系密切,在恶性肿瘤的进展过程中发挥一定的作用。此外,两者表达率高存在一定的相关性,经过统计学分析表明这两个蛋白之间存在一定的相互作用,协同增加肿瘤发展和转移几率。OPN和CD44阳性表达的患者术后5年生存率及无瘤生存率较二者表达阴性的患者低,表明二者的表达和患者预后密切相关,针对这两个蛋白可筛选出危险度高的患者,尽早采取适当针对个体的治疗。
[Abstract]:BACKGROUND AND OBJECTIVE: Hepatic metastasis of colorectal cancer is very common in patients with colorectal cancer, which greatly affects the survival time of patients after surgery and is difficult to cure clinically. However, there is no sensitive tumor marker for early diagnosis in patients with liver metastasis. Surgical resection can prolong the survival time of patients, but the resection rate is low. The pathogenesis of liver metastasis in colorectal cancer is very complex, involving multiple genes, chemokines, cytokines and multiple cellular pathways. The mechanism of liver metastasis has not been fully elucidated. Further study of its expression mediators will help to reveal the pathogenesis of colorectal cancer. Studies have shown that osteopontin mRNA and its related proteins are aggregated in colorectal benign tumors and malignant tumors, but are low-expressed in colorectal mucosa, and are involved in the occurrence of colorectal tumors from benign to malignant and the vicinity of malignant transformation. CD44 is one of the receptors of osteopontin in invasion and metastasis of colorectal cancer. It is expressed (+) in primary colorectal cancer and has a high expression rate. In addition, the expression rate of CD44 in metastatic mesangial lymphoid tissue is also increased, whereas in colorectal mucosa it is conversely expressed. Based on the above results, we hypothesized that OPN and CD44 expression were correlated with the degree and stage of malignancy, and could guide the prognosis of patients and targeted treatment. Methods: From January 2008 to December 2009, 76 cases of colorectal cancer or rectal cancer underwent total mesenteric radical resection in the General Surgical Center of Beijing Military Region General Hospital were collected, including the same samples. The expression of OPN and CD44 was detected by S-P method in 30 normal mucosa tissues adjacent to 10 cm of cancer and 16 liver metastasis tissues. The survival time of the patients was followed up. SPSS19.0 was used to process the expression of OPN. _2 test was used to compare the positive and negative groups of OPN and CD44. Results There were 53 cases (69.7%) with high expression of OPN, 40 cases (52.6%) with high expression of CD44, and 2 cases (30 cases) with high expression of OPN in normal mucosa adjacent to carcinoma. There were 5 cases (16.7%) with high expression of CD44, 12 cases (75.0%) with positive expression of OPN in 16 liver metastases and 11 cases (68.8%) with positive expression of CD44 in distant metastases. The positive expression rate of OPN and CD44 was higher in the tissues with tumor invasion of intestinal wall, lymph node metastasis and liver metastasis, while the expression rate of OPN was higher in the patients with poorly differentiated tumors. However, the expression of CD44 was not related to the degree of tumor differentiation. The 5-year survival rate of the patients with positive OPN and CD44 expression in colorectal adenocarcinoma was significantly lower than that of the patients with low OPN and CD44 expression. The difference was significant by statistical software analysis (P 0.05). Conclusion In colorectal adenocarcinoma, OPN and CD44 immunohistochemical colorectal cancer tissues showed significant difference. If the expression is high, the expression rate of both in the liver metastasis tissues is also high, and the expression rate of both in the above two tissues is significantly higher than that in the corresponding normal tissues. In addition, there is a certain correlation between the high expression rate of OPN and CD44. Statistical analysis shows that there is a certain interaction between the two proteins, which can increase the probability of tumor development and metastasis. The expression of these two proteins is closely related to the prognosis of patients. Individual therapy should be taken as soon as possible for patients with high risk.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.34

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