本文選題：腦膠質(zhì)瘤 + CRNDE��； 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:腦膠質(zhì)瘤是多種因素和多類基因相互作用后逐步發(fā)展的結(jié)果,但它具體的發(fā)生和發(fā)展機(jī)制仍是一個(gè)謎團(tuán)。長(zhǎng)鏈非編碼RNA(Lnc RNA)是構(gòu)成人類基因組中重要的組成部分,雖然其序列上缺乏開(kāi)放讀碼框(OFR),不能直接表達(dá)蛋白,但它在轉(zhuǎn)錄前后以及表觀遺傳學(xué)等多個(gè)環(huán)節(jié)對(duì)靶基因進(jìn)行精準(zhǔn)的調(diào)控。他通過(guò)間接干預(yù)基因的表達(dá)從而影響到整個(gè)生物學(xué)的功能。大量研究分析表明,Lnc RNA的異常表達(dá)與人類腫瘤的發(fā)生、演變有著緊密的關(guān)聯(lián),而且與腫瘤惡性分化程度以及預(yù)后相關(guān)。CRNDE是結(jié)腸癌差異表達(dá)長(zhǎng)鏈非編碼RNA,此基因存在于人染色體的反義鏈上,全長(zhǎng)約10kb,具有5個(gè)核心外顯子和一個(gè)附加外顯子。它在宮頸癌和直腸癌組織中的表達(dá)均明顯高于癌旁組織。這種表達(dá)差異在腦膠質(zhì)瘤中是否成立呢?本實(shí)驗(yàn)圍繞腦膠質(zhì)瘤組織與瘤旁組織,有關(guān)CRDNE表達(dá)水平是否存在差異以及CRNDE與腫瘤臨床病理學(xué)的關(guān)聯(lián)展開(kāi)研究,通過(guò)對(duì)兩組病人進(jìn)行長(zhǎng)期隨訪后,獲取他們的生存時(shí)間并納入生存分析。其結(jié)果可以為腦膠質(zhì)瘤病的診斷、治療及預(yù)后評(píng)估開(kāi)辟一條新的道路。方法:1收集自2007年至2012年,河北醫(yī)科大學(xué)第二醫(yī)院手術(shù)室,神經(jīng)外科手術(shù)當(dāng)中取出的膠質(zhì)瘤標(biāo)本。經(jīng)過(guò)我們仔細(xì)的核查后確認(rèn),全部的患者均未曾在術(shù)前接受過(guò)放射治療及化學(xué)藥物治療。留取進(jìn)行實(shí)驗(yàn)的組織均由病理科鑒定,存儲(chǔ)在凍存管內(nèi)并及時(shí)將管放入液氮罐內(nèi)保存。所收集的80例腦膠質(zhì)瘤標(biāo)本參照2007世界衛(wèi)生組織對(duì)中樞神經(jīng)系統(tǒng)(WHO-CNS)腫瘤的分類標(biāo)準(zhǔn),其中低級(jí)別組42例,高級(jí)別組38例。此外,在腦膠質(zhì)瘤手術(shù)當(dāng)中,收集20例手術(shù)入路中顯微鏡下距瘤組織邊緣1cm以內(nèi)的正常腦組織標(biāo)本(使用術(shù)中導(dǎo)航確定腫瘤邊界)作為對(duì)照組,收集方法與收集膠質(zhì)瘤組織一致。2使用實(shí)時(shí)熒光定量聚合酶鏈反應(yīng)(q RT-PCR)方法,獲取瘤旁組織與腦膠質(zhì)瘤組織的CRNDE表達(dá)量,并對(duì)兩者進(jìn)行比較。采用卡方檢驗(yàn)驗(yàn)證CRNDE表達(dá)水平與臨床病理特征的關(guān)系。經(jīng)過(guò)長(zhǎng)期隨訪,獲得腦膠質(zhì)瘤病人的生存時(shí)間,采用Kapaln-Meier生存分析,繪制兩組患者的生存曲線并對(duì)兩條曲線進(jìn)行比較,生存時(shí)間從患者手術(shù)之日算起,到其死亡或者是末次隨訪日所經(jīng)歷的時(shí)間,單位按月來(lái)計(jì)數(shù)。探索CRNDE表達(dá)水平的高低與患者五年生存率的關(guān)系。結(jié)果:1對(duì)比腦膠質(zhì)瘤組織與瘤旁組織的CRNDE表達(dá)水平,腦膠質(zhì)瘤組織中CRNDE的最后Ct均值為3.89±0.19,瘤旁組織CRNDE的最后Ct的均值為1.00±0.04,因此可以看出,CRNDE在腦膠質(zhì)瘤的表達(dá)水平明顯高于瘤旁組織CRNDE的表達(dá)水平。對(duì)比高級(jí)別腦膠質(zhì)瘤CRNDE的表達(dá)水平與低級(jí)別組CRNDE的表達(dá)水平,可發(fā)現(xiàn)高級(jí)別腫瘤CRNDE的最后Ct的均值為4.33±0.40,低級(jí)別腦膠質(zhì)瘤CRNDE的最后Ct均值為1.87±0.18,由此可知,高級(jí)別腦膠質(zhì)瘤組織當(dāng)中CRNDE的表達(dá)水平明顯高于低級(jí)別組。(見(jiàn)圖1、圖2、表1、表2)2對(duì)CRNDE的表達(dá)水平與患者年齡、性別、發(fā)病形式、腫瘤大小、是否存在壞死、WHO級(jí)別、腫瘤的復(fù)發(fā),多種臨床因素進(jìn)行比較,使用卡方檢驗(yàn)進(jìn)行分析后表明,CRNDE的表達(dá)與腫瘤的復(fù)發(fā)(P=0.010)、腫瘤的大小(P=0.026)、WHO分級(jí)(P=0.003)有關(guān),與年齡(P=0.358)、性別(P=0.204)、發(fā)病形式(P=0.171)、是否存在壞死(P=0.367)無(wú)關(guān)。(見(jiàn)表3)3本組資料中,我們根據(jù)CRNDE表達(dá)量選取中位表達(dá)量來(lái)劃分高表達(dá)組和低表達(dá)組。使用Kaplan-Meier進(jìn)行生存分析顯示,高表達(dá)組患者的生存時(shí)間較低表達(dá)組患者明顯縮短。比較兩者的一年生存率顯示:高表達(dá)組患者一年生存率為84.4%,低表達(dá)組患者一年生存率為97.1%,兩者比較有顯著差異(P0.05)。比較兩組患者五年生存率,發(fā)現(xiàn)CRNDE高表達(dá)組的腦膠質(zhì)瘤患者五年生存率僅為15.6%,低表達(dá)組患者五年的生存率為37.1%。兩者比較有顯著差異(P0.05)。(見(jiàn)圖3)結(jié)論:1在腦膠質(zhì)瘤組織與瘤旁組織有關(guān)CRNDE表達(dá)水平的對(duì)比中,以及高級(jí)別的腦膠質(zhì)瘤與低級(jí)別的腦膠質(zhì)瘤關(guān)于CRNDE表達(dá)水平的比較中,我們可以發(fā)現(xiàn)CRNDE在腦膠質(zhì)瘤組織中的表達(dá)明顯高于瘤旁組織中的表達(dá),且CRNDE的表達(dá)水平與WHO分級(jí)有關(guān),高級(jí)別的腦膠質(zhì)瘤CRNDE表達(dá)水平明顯高于低級(jí)組。2腦膠質(zhì)瘤中CRNDE表達(dá)水平與腫瘤的大小、WHO分級(jí)以及腫瘤是否復(fù)發(fā)有關(guān),與年齡、性別、發(fā)病形式、是否存在壞死因素?zé)o關(guān)。3腦膠質(zhì)瘤中CRNDE表達(dá)水平越高,往往相同時(shí)間內(nèi)其患者生存率越低,且CRNDE高表達(dá)組的患者五年生存率明顯小于低表達(dá)組。
[Abstract]:Objective: glioma is the result of gradual development of multiple factors and multiple genes interaction, but its specific occurrence and development mechanism is still a mystery. Long chain non coding RNA (Lnc RNA) is an important component of the human genome. Although the sequence lacks the open reading code frame (OFR), it can not express the protein directly, but it is in turn. A number of studies and analyses show that the abnormal expression of Lnc RNA is closely related to the occurrence and evolution of human tumor, and is closely related to the degree of malignant differentiation of the tumor and preconditioning. Post related.CRNDE is a differential expression of long chain noncoding RNA in colon cancer. This gene exists on the antisense chain of human chromosomes, with a total length of about 10KB, with 5 core exons and an additional exon. It is significantly higher in cervical and rectal cancer than in para cancerous tissues. The analysis of the difference in CRDNE expression and the association of CRNDE with the tumor clinicopathology of glioma tissue and paratumoral tissue, and the survival time and survival analysis after long-term follow-up to two groups of patients. The results can be used for the diagnosis, treatment and prognosis evaluation of brain glioma. A new way was established. Methods: 1 the specimens were collected from the operation room of the second hospital of Hebei Medical University from 2007 to 2012. After careful verification, we confirmed that all the patients had not been treated with radiation therapy and chemical therapy before the operation. Scientific identification, stored in the cryopreservation tube and stored in a liquid nitrogen tank in time. 80 specimens of glioma were collected with reference to the classification standard of the 2007 WHO for central nervous system (WHO-CNS) tumor, including 42 in low grade group and 38 in advanced group. In addition, 20 cases of surgical approach were collected during the operation of glioma. The normal brain tissue specimens (using intraoperative navigation to determine the tumor boundary) under the 1cm margin of the tumor tissue (using the intraoperative navigation to determine the tumor boundary) were used as the control group. The collection method was consistent with the collection of glioma tissues and used the real-time fluorescence quantitative polymerase chain reaction (Q RT-PCR) method to obtain the CRNDE expression of the paratumoral tissue and the brain gelatinous tumor tissue, and the two were compared. The relationship between the CRNDE expression level and the clinicopathological features was verified by chi square test. After long-term follow-up, the survival time of the patients with glioma was obtained. The survival curves of the two groups were plotted and compared with the two curves. The survival time was calculated from the day of the hand operation, to the death or the last follow-up day. The relationship between the level of CRNDE expression and the five year survival rate of patients was explored. Results: 1 compared with the expression level of CRNDE in brain glioma tissue and paratumoral tissue, the final Ct mean of CRNDE in glioma tissues was 3.89 + 0.19, and the mean value of final Ct of CRNDE in paratumoral tissue was 1 + 0.04, so it could be seen The expression level of CRNDE in glioma was significantly higher than that of CRNDE in the para tumor tissue. Compared with the expression level of CRNDE and the level of CRNDE in the low level group, the mean value of the final Ct of the high grade tumor CRNDE was 4.33 + 0.40, and the final Ct of the low grade glioma CRNDE was 1.87 + 0.18. The level of CRNDE expression in the advanced glioma tissues was significantly higher than that in the low level group. (see Figure 1, figure 2, table 1, table 2) 2 CRNDE expression levels were compared with patient's age, sex, form, size, necrosis, WHO level, tumor recurrence, multiple clinical factors, and analysis of CRNDE by chi square test. CRNDE The expression is related to tumor recurrence (P=0.010), tumor size (P=0.026), WHO classification (P=0.003), not related to age (P=0.358), sex (P=0.204), pathogenesis (P=0.171) and necrosis (P=0.367). (see Table 3) 3 in the data of this group, we divide the high expression and low expression groups according to the median expression of CRNDE expression. Use Kapla. N-Meier survival analysis showed that the survival time of the high expression group was significantly shortened. The one year survival rate of the two groups showed that the one year survival rate in the high expression group was 84.4%, the one year survival rate in the low expression group was 97.1%, and the difference was significant (P0.05). The five year survival rate of the two groups was compared with that of the two groups. The five year survival rate of the E high expression group was only 15.6%, and the five year survival rate of the low expression group was 37.1%. (P0.05). (see Figure 3) conclusion: 1 in the comparison of the level of CRNDE expression in the brain glioma tissue and the paratumoral tissue, and the high grade glioma and the low grade glioma on CRNDE In the comparison of the expression level, we can find that the expression of CRNDE in the glioma tissue is significantly higher than that in the para tumor tissue, and the expression level of CRNDE is related to the WHO classification. The level of CRNDE expression in the high grade glioma is significantly higher than the level of CRNDE in the.2 glioma of the low-grade group and the size of the tumor, WHO classification and the tumor are the same. The higher the level of CRNDE expression in.3 glioma is not related to age, sex, form of disease, and whether there is a necrosis factor, the lower the survival rate of the patients in the same time, and the five year survival rate in the CRNDE high expression group is significantly smaller than that in the low expression group.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R739.41

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