长链非编码RNA与糖尿病合并结直肠癌的相关性分析

发布时间：2018-06-03 21:45

本文选题：2型糖尿病 + 长链非编码RNA　；参考：《宁波大学》2017年硕士论文

【摘要】：目的:初步研究长链非编码RNA(long non-coding RNA,lncRNA)MALAT1、linc RNA-p21和H19在T2DM合并结直肠癌(colorectal cancer,CRC)患者组织中的表达水平,及其与患者临床病理特征之间的关联性。从分子水平探讨T2DM和CRC发生发展之间的关系,以期为T2DM人群易发CRC的早期预警提供理论依据。方法:(1)收集34例单纯CRC患者的新鲜癌组织,并取其癌旁5cm的正常结直肠黏膜组织作为对照;另选取361例不同血糖水平的CRC病例,收集其石蜡组织样本及相关临床病理资料;(2)采用荧光定量PCR方法检测MALAT1、linc RNA-p21和H19在组织中的表达情况,分析lnc RNA之间的线性相关关系,并应用Logistic回归分析对混杂因素进行校正,探究三个lnc RNA表达水平与患者临床病理特征之间的关联性。结果:(1)在34对单纯CRC及其对应的癌旁正常结直肠黏膜组织中,MALAT1与H19在在单纯CRC组相对于正常组织中均呈高表达(t=7.71,P=6.95×10-9;t=5.83,P=1.59×10-6);linc RNA-p21在CRC组织中呈低表达状态(t=-4.39,P=1.10×10-4);(2)在361例不同血糖水平的CRC患者石蜡组织中,MALAT1、linc RNAp21在组间表达差异无统计学意义,H19在三组间表达水平具有统计学差异(F=7.00,P=0.001);(3)经LSD法分析发现,Pre-DM+CRC组和T2DM+CRC组中H19的表达水平均低于单纯CRC组(P0.05)。Logistic回归对混杂因素校正后发现,与单纯CRC组相比,Pre-DM+CRC组中H19的表达水平降低(Adjusted OR(AOR)=1.219,95%CI=1.055-1.408,P=0.007),T2DM+CRC组中H19仍是低表达状态(AOR=1.322,95%CI=1.024-1.706,P=0.032);(4)在144例单纯CRC组中,MALAT1的表达水平与H19的表达呈正相关(r=0.297,P=3.028×10-4),linc RNA-p21的表达与H19的表达也呈正相关(r=0.437,P=4.511×10-8);在160例Pre-DM+CRC组中,MALAT1的表达情况与H19呈正相关(r=0.329,P=2.190×10-5);在57例T2DM+CRC组中,MALAT1的表达与H19呈正相关关系(r=0.313,P=0.018);linc RNAp21的表达水平与H19则呈显著的负相关关系(r=-0.660,P=2.286×10-8);(5)在单纯CRC组中,高血压患者的H19表达水平高于非高血压患者(t=2.07,P=0.040)。结论:1、MALAT1、linc RNA-p21和H19均参与了CRC的发生发展过程,其中MALAT1和H19是促癌因子,linc RNA-p21在CRC的发病中起保护作用。2、H19在血糖异常的CRC组织中表达水平下调,糖尿病可能导致H19与linc RNA-p21相关关系的方向发生改变。3、高血压可能会影响H19在CRC患者中的表达水平。
[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.
【学位授予单位】：宁波大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1;R735.34

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