维生素D水平及其受体mRNA表达与结直肠腺瘤和腺癌的意义的研究

发布时间：2019-04-27 11:44

【摘要】：研究目的:大量研究表明维生素D与维生素D受体(VDR)结合后具有抗肿瘤的作用。本研究通过比较结直肠腺癌患者、结直肠腺瘤患者及正常人外周血单个有核细胞(PBMC)中及组织中维生素D受体mRNA的表达情况,旨在探讨VDR mRNA变化是否参与结直肠肿瘤的发生。比较三种受试者血浆中维生素D浓度,验证维生素D缺乏是否为结直肠癌及腺瘤发病的危险因素。此外结合临床资料分析血浆维生素D水平、组织VDR mRNA及PBMC中的VDR mRNA与患者一般资料及病理资料的关系。研究方法:本实验主要采用病例-对照设计。利用ELISA法测定正常组、结直肠腺瘤组、结直肠腺癌组患者的血浆中25-OH-D浓度,采用实时荧光定量PCR技术测定PBMC及组织中维生素D受体的表达水平并用2^-ΔΔCt法或ΔCt法量化VDR mRNA的表达量。比较血浆维生素D、组织VDR mRNA及PBMC中的VDR mRNA在健康志愿者、腺瘤患者、腺癌患者中的情况,并分析以上指标与临床资料及病理资料的关系。结果:1、结直肠腺癌组织中维生素D受体表达明显低于癌旁组织(P0.01);正常结直肠组织中VDR mRNA表达水平明显高于结直肠腺癌(P0.01)和结直肠腺瘤组织(P0.01),但是结直肠腺瘤与结直肠腺癌中VDR mRNA表达差异并不存在统计学意义(P=0.106);VDR mRNA在腺瘤中的表达与患者年龄、性别、腺瘤瘤变程度、病理类型等均不相关;VDR mRNA在腺癌中的表达与腺癌患者的性别、年龄、肿瘤分化程度、大小、转移等均不相关。2、PBMC VDR mRNA的表达在正常人群、腺瘤及腺癌中差异并无统计学意义(P=0.7)。3、正常人的维生素D水平明显高于结直肠癌(P0.01)与结直肠腺瘤患者(P0.01),而结直肠癌和结直肠腺瘤的维生素D水平无明显差异(P=0.489);低维生素D水平作为结直肠腺瘤及结直肠腺癌的危险因素OR值分别为4.875和2.925。4、我们还发现正常人中血浆维生素D浓度可能与PBMC中VDR mRNA的表达量呈负相关,相关系数r=0.408,回归方程Y(vitamin D)=2.846X(VDRΔCt)-13.585,但在腺瘤及腺癌患者中并不存在两者并不存在相关性。结论:结直肠腺瘤及腺癌组织VDR mRNA表达水平降低可能与结直肠腺癌及结直肠腺瘤的发生相关,但与结直肠腺瘤的病理类型、瘤变程度等不相关,与腺癌的分化程度、转移、大小、浸润深度等均不相关。外周血单个有核细胞VDR mRNA的表达水平与腺瘤及腺癌无关,在腺瘤患者中。维生素D水平降低可能与结直肠腺癌及结直肠腺瘤的发生发展相关;低血浆维生素D水平可能是结直肠腺癌和结直肠腺瘤的危险因素。综上,研究表明维生素D缺乏和VDR mRNA降低共同作用于结直肠腺癌和结直肠腺瘤的发生发展,为研究结直肠癌的致病机制提供了新的线索。
[Abstract]:Objective: a large number of studies have shown that vitamin D binding to vitamin D receptor (VDR) has anti-tumor effect. The aim of this study was to compare the expression of vitamin D receptor mRNA in peripheral blood mononuclear cells (PBMC) and tissues of patients with colorectal adenocarcinoma, colorectal adenomas and normal controls. The purpose of this study was to investigate whether the changes of VDR mRNA were involved in the development of colorectal tumors. Compare plasma vitamin D concentrations in three subjects to verify whether vitamin D deficiency is a risk factor for colorectal cancer and adenoma. In addition, the relationship between plasma vitamin D level, VDR mRNA in tissue VDR mRNA and PBMC and the general data and pathological data of the patients was analyzed with clinical data. Research methods: case-control design was used in this experiment. The plasma levels of 25-OH-D in normal group, colorectal adenomas group and colorectal adenocarcinoma group were measured by ELISA method. The expression level of vitamin D receptor in PBMC and tissues was determined by real-time fluorescence quantitative PCR and the expression of VDR mRNA was quantified by 螖-Ct or 螖 Ct. The levels of plasma vitamin D, tissue VDR mRNA and PBMC VDR mRNA in healthy volunteers, adenoma patients and adenocarcinoma patients were compared, and the relationship between the above indexes and clinical and pathological data was analyzed. Results: 1. The expression of vitamin D receptor in colorectal adenocarcinoma was significantly lower than that in paracancerous tissues (P0.01). The expression level of VDR mRNA in normal colorectal tissue was significantly higher than that in colorectal adenocarcinoma (P0.01) and colorectal adenoma (P0.01), but there was no significant difference in VDR mRNA expression between colorectal adenoma and colorectal adenocarcinoma (P < 0. 106). The expression of VDR mRNA in adenomas was not correlated with age, sex, degree of adenomatosis, pathological type and so on. The expression of VDR mRNA in adenocarcinoma was not correlated with sex, age, tumor differentiation, size, metastasis and so on. 2. There was no significant difference in the expression of VDR mRNA among normal population, adenoma and adenocarcinoma (P < 0. 7), and there was no significant difference in the expression of PBMCs in adenomas, adenomas and adenocarcinomas (P < 0. 7). The levels of vitamin D in normal subjects were significantly higher than those in patients with colorectal cancer (P0.01) and colorectal adenoma (P0.01), but there was no significant difference in vitamin D levels between colorectal cancer and colorectal adenoma (P < 0. 489). The OR values of low vitamin D level as risk factors for colorectal adenoma and colorectal adenocarcinoma were 4.875 and 2.925.4, respectively. We also found that the plasma vitamin D concentration in normal subjects may be negatively correlated with the expression of VDR mRNA in PBMC. The correlation coefficient was r = 0.408, the regression equation Y (vitamin D) = 2.846X (VDR 螖 Ct)-13.585, but there was no correlation between them in adenomas and adenocarcinomas. Conclusion: the decreased expression of VDR mRNA in colorectal adenomas and adenocarcinomas may be related to the occurrence of colorectal adenomas and colorectal adenomas, but it is not correlated with the pathological types and tumorigenesis of colorectal adenomas, and may be associated with the differentiation and metastasis of adenocarcinomas, and may be associated with the development of colorectal adenomas and colorectal adenomas. The size and depth of infiltration were not correlated. The expression of VDR mRNA in peripheral blood mononuclear cells was not correlated with adenomas and adenocarcinomas. The decrease of vitamin D level may be related to the development of colorectal adenocarcinoma and colorectal adenoma, and low plasma vitamin D level may be a risk factor for colorectal adenocarcinoma and colorectal adenoma. In summary, it is suggested that vitamin D deficiency and decreased VDR mRNA play an important role in the development of colorectal adenocarcinoma and colorectal adenoma, which provides a new clue to study the pathogenesis of colorectal cancer.
【学位授予单位】：宁波大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.34

【相似文献】