【摘要】：背景與目的:結直腸癌肝轉(zhuǎn)移在結直腸癌患者中十分常見,極大影響患者術后生存期,臨床上難以治愈,然而目前對于肝轉(zhuǎn)移的患者缺乏早期診斷的敏感腫瘤標志物,治療上雖然手術切除能延長患者一定的生存時間,但手術切除率較低,難以完全切凈病灶,治療效果不佳,缺乏有效地靶向治療藥物。結直腸癌肝轉(zhuǎn)移的發(fā)病機制十分復雜,涉及多個基因、趨化因子,細胞因子及多條細胞通路等,目前對其機制的研究尚未完全闡明,進一步研究其表達的介質(zhì),有助于揭示結直腸癌肝轉(zhuǎn)移的影響因素,指導臨床工作。研究證實,骨橋蛋白的mRNA以及其相應的表達的蛋白在結直腸良性腫瘤以及惡性腫瘤的組織中集聚,而在結直腸黏膜組織中呈現(xiàn)低表達,其參與結直腸腫瘤從良性到惡性的發(fā)生以及惡變后的周圍侵襲及轉(zhuǎn)移,CD44是骨橋蛋白的受體之一,其在結直腸癌原發(fā)灶中呈表達(+),且表達率較高,此外,在轉(zhuǎn)移的系膜淋巴組織中的表達率也升高,而在結直腸黏膜組織中表達則相反,研究結果表明,CD44參與細胞遷移,經(jīng)過激活各種信號通路增加腫瘤細胞增殖和遠處轉(zhuǎn)移的幾率�；谝陨涎芯砍晒�,我們推測OPN與CD44的表達存在一定相關性,并且與腫瘤的惡性程度及分期有關,能指導患者預后及針對性治療。研究結果有望進一步闡明OPN與CD44與臨床病理的關系以及二者的相關性和對預后的指導意義,為臨床治療結直腸癌肝轉(zhuǎn)移提供新的靶點及治療方法。方法:病例采集2008年1月至2009年12月于北京軍區(qū)總醫(yī)院全軍普通外科中心經(jīng)全系膜根治性切除手術治療的結腸癌或者直腸癌患者的組織標本76例,包括取同一患者標本的癌旁10cm處的正常黏膜組織30例,肝臟轉(zhuǎn)移癌組織16例進行S-P法檢測OPN與CD44在上述標本中的表達情況,隨訪患者的生存期,使用統(tǒng)計學軟件SPSS19.0進行處理,OPN陽性和陰性組、CD44陽性與陰性組之間的比較用χ2檢驗,組間比較經(jīng)統(tǒng)計學軟件分析后P值小于0.05為差異有意義,患者術后5年生存率用Kplan-Meier曲線進行分析,比較二者表達對預后的影響。結果76例結直腸癌組織中OPN高表達的有53例(69.7%),CD44高表達的有40例(52.6%),30例癌旁正常黏膜組織中高表達OPN的有2例(6.7%),高表達CD44的有5例(16.7%),16例肝臟轉(zhuǎn)移灶中OPN表達陽性的有12(75.0%)例,CD44在遠處轉(zhuǎn)移灶中表達陽性的有11(68.8%)例。OPN和CD44在CC的腺癌組織中及其肝臟轉(zhuǎn)移組織中呈現(xiàn)表達升高的現(xiàn)象,而正常黏膜則相反,二者的差別經(jīng)過統(tǒng)計學分析,有統(tǒng)計學意義(P0.001)。OPN與CD44表達陽性的患者,在腫瘤侵犯腸壁的深度增加、淋巴結轉(zhuǎn)移陽性以及肝轉(zhuǎn)移陽性的組織中,陽性表達率高,而腫瘤分化差的患者OPN表達率高,但是,CD44表達程度的高低與腫瘤的分化程度無關。OPN與CD44在結直腸癌原發(fā)灶特別是肝轉(zhuǎn)移灶中的高表達有明顯相關性。OPN和CD44在結直腸腺癌組織中表達陽性的患者術后5年生存率較OPN和CD44表達低的患者明顯下降,經(jīng)統(tǒng)計學軟件分析,差異顯著(P0.05)。結論在結直腸腺癌組織中,OPN與CD44免疫組化結果為高表達,在其肝臟轉(zhuǎn)移組織中,二者表達率也很高,并且二者在上述兩種組織中的表達率顯著高于對應的正常組織中的表達,因此,二者在原發(fā)灶及轉(zhuǎn)移癌組織中的表達率高與惡性腫瘤局部浸潤和遠處轉(zhuǎn)移關系密切,在惡性腫瘤的進展過程中發(fā)揮一定的作用。此外,兩者表達率高存在一定的相關性,經(jīng)過統(tǒng)計學分析表明這兩個蛋白之間存在一定的相互作用,協(xié)同增加腫瘤發(fā)展和轉(zhuǎn)移幾率。OPN和CD44陽性表達的患者術后5年生存率及無瘤生存率較二者表達陰性的患者低,表明二者的表達和患者預后密切相關,針對這兩個蛋白可篩選出危險度高的患者,盡早采取適當針對個體的治療。
[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.
【學位授予單位】：第三軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R735.34

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相關期刊論文 前1條

1 Yick Liang Lum;Ester Khin;Nikki P Lee;John M Luk;;Osteopontin as potential biomarker and therapeutic target in gastric and liver cancers[J];World Journal of Gastroenterology;2012年30期

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本文編號：2248913