長鏈非編碼RNA與糖尿病合并結(jié)直腸癌的相關(guān)性分析
本文選題:2型糖尿病 + 長鏈非編碼RNA; 參考:《寧波大學》2017年碩士論文
【摘要】:目的:初步研究長鏈非編碼RNA(long non-coding RNA,lncRNA)MALAT1、linc RNA-p21和H19在T2DM合并結(jié)直腸癌(colorectal cancer,CRC)患者組織中的表達水平,及其與患者臨床病理特征之間的關(guān)聯(lián)性。從分子水平探討T2DM和CRC發(fā)生發(fā)展之間的關(guān)系,以期為T2DM人群易發(fā)CRC的早期預警提供理論依據(jù)。方法:(1)收集34例單純CRC患者的新鮮癌組織,并取其癌旁5cm的正常結(jié)直腸黏膜組織作為對照;另選取361例不同血糖水平的CRC病例,收集其石蠟組織樣本及相關(guān)臨床病理資料;(2)采用熒光定量PCR方法檢測MALAT1、linc RNA-p21和H19在組織中的表達情況,分析lnc RNA之間的線性相關(guān)關(guān)系,并應用Logistic回歸分析對混雜因素進行校正,探究三個lnc RNA表達水平與患者臨床病理特征之間的關(guān)聯(lián)性。結(jié)果:(1)在34對單純CRC及其對應的癌旁正常結(jié)直腸黏膜組織中,MALAT1與H19在在單純CRC組相對于正常組織中均呈高表達(t=7.71,P=6.95×10-9;t=5.83,P=1.59×10-6);linc RNA-p21在CRC組織中呈低表達狀態(tài)(t=-4.39,P=1.10×10-4);(2)在361例不同血糖水平的CRC患者石蠟組織中,MALAT1、linc RNAp21在組間表達差異無統(tǒng)計學意義,H19在三組間表達水平具有統(tǒng)計學差異(F=7.00,P=0.001);(3)經(jīng)LSD法分析發(fā)現(xiàn),Pre-DM+CRC組和T2DM+CRC組中H19的表達水平均低于單純CRC組(P0.05)。Logistic回歸對混雜因素校正后發(fā)現(xiàn),與單純CRC組相比,Pre-DM+CRC組中H19的表達水平降低(Adjusted OR(AOR)=1.219,95%CI=1.055-1.408,P=0.007),T2DM+CRC組中H19仍是低表達狀態(tài)(AOR=1.322,95%CI=1.024-1.706,P=0.032);(4)在144例單純CRC組中,MALAT1的表達水平與H19的表達呈正相關(guān)(r=0.297,P=3.028×10-4),linc RNA-p21的表達與H19的表達也呈正相關(guān)(r=0.437,P=4.511×10-8);在160例Pre-DM+CRC組中,MALAT1的表達情況與H19呈正相關(guān)(r=0.329,P=2.190×10-5);在57例T2DM+CRC組中,MALAT1的表達與H19呈正相關(guān)關(guān)系(r=0.313,P=0.018);linc RNAp21的表達水平與H19則呈顯著的負相關(guān)關(guān)系(r=-0.660,P=2.286×10-8);(5)在單純CRC組中,高血壓患者的H19表達水平高于非高血壓患者(t=2.07,P=0.040)。結(jié)論:1、MALAT1、linc RNA-p21和H19均參與了CRC的發(fā)生發(fā)展過程,其中MALAT1和H19是促癌因子,linc RNA-p21在CRC的發(fā)病中起保護作用。2、H19在血糖異常的CRC組織中表達水平下調(diào),糖尿病可能導致H19與linc RNA-p21相關(guān)關(guān)系的方向發(fā)生改變。3、高血壓可能會影響H19在CRC患者中的表達水平。
[Abstract]:Objective: to study the expression level of long chain noncoding RNA(long non-coding RNA-lncRNA-MALAT1linc RNA-p21 and H19 in patients with T2DM complicated with colorectal cancer and its correlation with clinicopathological features. The relationship between the occurrence and development of T2DM and CRC was discussed at molecular level in order to provide a theoretical basis for early warning of CRC in T2DM population. Methods fresh cancer tissues of 34 patients with simple CRC were collected and the normal colorectal mucosa tissues of adjacent 5cm were collected as control, and 361 CRC cases with different blood glucose levels were selected. The paraffin tissue samples and clinicopathological data were collected to detect the expression of MALAT1 linc RNA-p21 and H19 by fluorescence quantitative PCR. The linear correlation between lnc RNA was analyzed, and the confounding factors were corrected by Logistic regression analysis. To explore the correlation between the three levels of lnc RNA expression and the clinicopathological features of patients. Results in 34 pairs of simple CRC and its corresponding normal colorectal mucosa tissues, malat 1 and H19 were highly expressed in 34 pairs of normal colorectal mucosa tissues compared with normal tissues in the simple CRC group. The expression of Tet 7. 71% was higher than that in the normal tissues. The expression of Mal 1 and H19 in 34 pairs of simple CRC and its corresponding normal colorectal mucosa tissues was 6. 95 脳 10 ~ (-9) 脳 10 ~ (-9) RNA-p21 and 1. 59 脳 10 ~ (-6) RNA-p21 in CRC tissues.) in 361 cases of different blood glucose water, the expression level of MALAT1 and H19 was 1. 10 脳 10 ~ (-4) and 1.10 脳 10 ~ (-4), respectively. There was no significant difference in the expression of H19 in paraffin tissues of patients with CRC. There was no significant difference in the expression level of H19 among the three groups. LSD analysis showed that the expression levels of H19 in pre-DM CRC group and T2DM CRC group were lower than those in CRC group. Logistic regression was used to correct the confounding factors. The expression of H19 in Pre-DM CRC group is lower than that in CRC group. There is a positive correlation between H19 expression and H19 expression in CRC group. The expression level of H19 is positively correlated with the expression of H19 0.297P3.028 脳 10 ~ (-4) T2DM CRC group and H19 expression in 144 cases of simple CRC group (CI 1.024-1.706 P0.032 ~ (1) and the expression of H19 is also positively correlated with the expression of H19. The expression of H19 is also positively correlated with the expression of H19 in the CRC group with a low expression of AOR1 1.322 + 95% CI1.024-1.706 P0.032 ~ (1) in 144 cases of simple CRC group, the expression of H19 is positively correlated with the expression of rmna 0.297P3.028 脳 10 ~ (-4) TDM CRC group. The expression of MALAT1 was positively correlated with H19 in 160 cases of Pre-DM CRC, and was positively correlated with that of H19 in 57 cases of T2DM CRC. In 57 cases of T2DM CRC, there was a positive correlation between the expression of MALAT1 and H19, and there was a significant negative correlation between the expression level of MALAT1 and H19) in the group of CRC alone, there was a significant negative correlation between the expression of MALAT1 and H19, and the positive correlation between the expression of MALAT1 and H19 was negative correlation with H19, and the positive correlation was found between the expression of MALAT1 and H19 in 57 cases of T2DM CRC, and the positive correlation between the expression of MALAT1 and H19 was negative correlation between the expression of MALAT1 and H19, and the positive correlation between the expression of MALAT1 and H19 was significant. The expression level of H 19 in hypertensive patients was higher than that in non hypertensive patients. Conclusion both RNA-p21 and H19 participate in the occurrence and development of CRC. MALAT1 and H19 play a protective role in the pathogenesis of CRC. The expression of H19 is down-regulated in CRC with abnormal blood glucose. Diabetes may lead to a change in the direction of the relationship between H19 and linc RNA-p21. Hypertension may affect the expression of H19 in CRC patients.
【學位授予單位】:寧波大學
【學位級別】:碩士
【學位授予年份】:2017
【分類號】:R587.1;R735.34
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