甘露糖受体和miRNA-1260b在胃肠道肿瘤中预后价值的研究

发布时间：2018-05-28 08:20

本文选题：胃癌 + 甘露糖受体　；参考：《兰州大学》2017年博士论文

【摘要】：目的:1.第一部分通过对120例胃癌手术患者的临床资料进行整理,研究甘露糖受体(MR)在胃癌组织中的表达及与临床特征之间的关系,进一步分析其与胃癌患者生存时间之间的关系,评价其在临床预后中的价值。2.第二部分研究120例CRC患者miR-1260b表达及与临床病理特征的关系,分析miR-1260b与结肠癌患者生存时间之间关系,评价其在临床预后中的价值。方法:1.分别对120例胃癌患者的癌组织及相应癌旁组织使用免疫组织化学及RT-PCR分析法测定甘露糖受体的表达。根据染色强度得分将患者分为甘露糖受体低表达组与甘露糖受体高表达组。采用卡方检验分析甘露糖受体的表达与临床病理特征之间的关系。Kaplan-Meier法(基于甘露糖受体表达数据)绘制生存曲线,两组间的生存期差异采用Log-rank检验比较。总生存期(OS)和无病生存期(DFS)为主要结果。并通过单因素及多因素COX回归模型分析甘露糖受体的表达与生存时间的的关系。对收集的120对CRC组织样本,采用Real-time PCR检测miR-1260b的表达。根据中间值分为二组,分析CRC组织中miR-1260b高表达与临床病理特征之间的关系。生存分析采用Kaplan-Meier法绘制生存曲线,两组间的生存期的差异log-rank检验比较。并通过单因素及多因素COX回归模型分析miR-1260b的表达与生存时间的关系。结果:第一部分甘露糖受体在胃癌中预后价值的研究1.胃癌组织中甘露糖受体的表达,根据染色强度得分把患者分为两组:甘露糖受体低表达组与甘露糖受体高表达组。甘露糖受体蛋白在胃癌细胞中的表达率高达45.8%(54/120),显著高于癌旁组织20%(36/120)(χ2=6.286,P=0.012)。为了进一步验证免疫组化结果,采用PT-PCR检测甘露糖受体mRNA的表达水平。随机选择了30例患者,分别取胃癌组织及相应癌旁组织。30对样本中的19例显示,与相应癌旁组织相比,胃癌组织中的甘露糖受体mRNA表达增加2倍以上,最高增加14.7倍。2.胃癌组织中甘露糖受体与患者的临床病理特征之间的关系甘露糖受体高表达与胃癌患者临床病理特征中的肿瘤大小、T分期、N分期及UICC分期有统计学意义(P0.05)。而与胃癌患者的年龄、性别、M分期、肿瘤定位、Lauren分型、淋巴管浸润,及术后化疗与甘露糖受体表达没有统计学意义(P0.05)。3.甘露糖受体表达与胃癌患者的预后Kaplan-Meier生存曲线表明,甘露糖受体高表达组患者的DFS与OS均明显短于甘露糖受体低表达组患者(log-rank P0.05)。采用COX回归模型,分析影响胃癌患者DFS和OS的每个变量。单因素分析结果提示胃癌患者预后与甘露糖受体表达水平密切相关。多因素分析结果表明:甘露糖受体的高表达是胃癌患者预后不良的独立影响因素。第二部分miRNA-1260b在结直肠癌中预后价值的研究1.结直肠癌组织与正常组织miR-1260b表达及有、无淋巴结转移患者结直肠癌组织miR-1260b表达水平CRC组织中mi R-1260b的表达显著高于相应癌旁组织中miR-1260b的表达水平(P0.001)。按淋巴结有、无转移分两组,分析不同淋巴结状态患者miR-1260b表达水平。与无淋巴结转移患者相比,发生淋巴结转移的患者CRC组织miR-1260b表达水平有统计学意义(P0.001)。2.miR-1260b表达与临床病理特征之间的关系根据mi R-1260b表达水平(2-ΔΔ中位数为中间值),将120例CRC患者分为miR-1260b高表达组与miR-1260b低表达组。即分为:67例高表达组CRC患者和53例低表达组CRC患者。分析CRC患者的临床病理特征与miR-1260b表达之间的关系。我们发现,高表达miR-1260b的CRC患者与淋巴结转移(P0.05)及静脉浸润(P0.001)有统计学意义。而与其它的临床参数,如年龄、性别、肿瘤的大小、分化程度、浸润的深度及肿瘤的位置无统计学意义(P0.05)。3.miR-1260b表达与CRC患者的预后我们采用Kaplan-Meier方法绘制所有患者生存曲线(DFS和OS)。结果表明,患者miR-1260b高表达的CRC生存时间明显低于mi R-1260b低表达水平的CRC者。单因素分析显示,静脉浸润(P0.05)、肿瘤浸润深度、淋巴结转移以及高miR-1260b表达水平(P0.01)与OS统计学意义。采用COX回归模型进行多因素分析,提示miR-1260b高表达预示着患者的预后不良。结论:1.通过甘露糖受体在胃癌组织中的高表达及临床病理特征之间的关系,我们推测甘露糖受体可能促进胃癌细胞的生长、增殖和侵袭,恶性程度与甘露糖受体的表达呈正相关。与甘露糖受体低表达的患者相比,甘露糖受体高表达患者的生存时间短。多因素回归分析表明,甘露糖受体高表是患者预后不良的一个独立影响因素,可能是胃癌患者预后不良的潜在肿瘤标志物。2.我们发现结直肠中癌组织及淋巴结转移患者miR-1260b高表达,同时结合与临床病理特征之间的关系分析,其与淋巴结转移及静脉浸润有统计学意义,这意味着miR-1260b可能促进了结直肠癌的早期转移。miR-1260b高表达的患者的生存时间比低表达者短,采用COX回归单因素分析mi R-1260b与生存时间之间有相关性,进行多因素分析,表明miR-1260b高表达是患者预后不良的一个独立影响因素,可作为患者预后不良的潜在肿瘤标志物。
[Abstract]:Objective: 1. to investigate the relationship between the expression of mannose receptor (MR) in gastric cancer tissue and its relationship with the clinical features in 120 cases of gastric cancer surgery, and to further analyze the relationship between it and the survival time of gastric cancer patients and evaluate the value of.2. second in the clinical prognosis of the patients, and to study 120 cases of CRC patients. The relationship between the expression of miR-1260b and the clinicopathological features, the relationship between the miR-1260b and the survival time of the patients with colon cancer, and the value of its clinical prognosis. Methods: 1. the expression of mannose receptor was measured by immunohistochemistry and RT-PCR analysis in 120 cases of gastric cancer and the corresponding para cancerous tissue. The color intensity score was divided into the low expression group of mannose receptor and the high expression group of mannose receptor. The relationship between the expression of mannose receptor and the clinicopathological features was analyzed by chi square test. The survival curve was drawn by.Kaplan-Meier method (based on mannose receptor expression data), and the difference of survival time between the two groups was compared by Log-rank test. The survival time (OS) and the disease-free survival (DFS) were the main results. The relationship between the expression of mannose receptor and the survival time was analyzed by single factor and multiple factor COX regression model. The expression of miR-1260b was detected by Real-time PCR in the samples of 120 pairs of CRC tissues. The high expression of miR-1260b in CRC tissues was analyzed in two groups according to the median value. The relationship between the clinical and pathological features. Survival analysis was made by Kaplan-Meier method to draw the survival curve and the difference of the survival time between the two groups. The relationship between the expression of miR-1260b and the survival time of miR-1260b was analyzed by single factor and multiple factor COX regression model. Results: the first part of the mannose receptor in the prognosis of gastric cancer The expression of mannose receptor in 1. gastric carcinoma was divided into two groups: mannose receptor low expression group and mannose receptor high expression group. The expression rate of mannose receptor protein in gastric cancer cells was 45.8% (54/120), which was significantly higher than that of para cancerous tissue 20% (36/120) (x 2=6.286, P=0.012). The expression level of mannose receptor mRNA was detected by PT-PCR. 30 patients were selected randomly, and 19 cases of gastric carcinoma tissue and corresponding paracancerous tissue.30 were selected respectively. The expression of mannose receptor mRNA in gastric carcinoma tissue increased more than 2 times compared with the corresponding para cancerous tissue, and the highest increase of manna in.2. gastric cancer tissue was 14.7 times. The relationship between the glucose receptor and the clinicopathological features of the patients was significant with the tumor size, T staging, N staging and UICC staging in the clinicopathological features of gastric cancer patients (P0.05). The age, sex, M stage, tumor location, Lauren typing, lymphatic infiltration, and postoperative chemotherapy and mannose receiving in patients with gastric cancer. There was no statistical significance (P0.05).3. mannose receptor expression and the prognosis of gastric cancer patients with Kaplan-Meier survival curve, indicating that the DFS and OS in the mannose receptor high expression group were significantly shorter than those of the mannose receptor low expression group (log-rank P0.05). COX regression model was used to analyze each variable that affects the DFS and OS of the gastric cancer patients. The result of factor analysis indicates that the prognosis of gastric cancer patients is closely related to the level of mannose receptor expression. The results of multifactor analysis show that the high expression of mannose receptor is an independent factor in the prognosis of gastric cancer patients. Second the study of the prognostic value of second part of the colorectal cancer in the colorectal cancer 1. colorectal cancer tissue and normal tissue of normal tissues The expression level of MI R-1260b in the miR-1260b expression level of colorectal cancer tissues without lymph node metastasis was significantly higher than that of miR-1260b in the adjacent tissues (P0.001). There were two groups of lymph nodes and no metastases, and the expression level of miR-1260b in the patients with different lymph node states was analyzed. Compared with those without lymph node metastasis, the R-1260b was compared with those in the patients with no lymph node metastases. The expression level of miR-1260b in CRC tissue was statistically significant (P0.001) and the relationship between the expression of.2.miR-1260b and the clinicopathological features was based on the level of MI R-1260b expression (the median of 2- delta delta), and 120 cases of CRC patients were divided into miR-1260b high expression group and miR-1260b low expression group. That is, 67 cases of high expression group were CRC. The relationship between the clinicopathological features of the CRC patients and the expression of miR-1260b was analyzed in 53 patients with low expression of CRC. We found that the CRC patients with high expression of miR-1260b were statistically significant with lymph node metastasis (P0.05) and venous infiltration (P0.001), and with other clinical parameters, such as age, sex, tumor size, degree of differentiation, depth of infiltration. The location of the degree and tumor was not statistically significant (P0.05).3.miR-1260b expression and the prognosis of CRC patients. We used Kaplan-Meier method to draw all patients' survival curves (DFS and OS). The results showed that the survival time of miR-1260b high expression of CRC was significantly lower than that of MI R-1260b low expression of CRC. Single factor analysis showed that the venous infiltration (P0.05) was the single factor analysis. The depth of tumor invasion, lymph node metastasis and high miR-1260b expression level (P0.01) and OS were statistically significant. Multifactor analysis was carried out by COX regression model, suggesting that high expression of miR-1260b indicates poor prognosis of patients. Conclusion: 1. we push the relationship between high expression of mannose receptor in gastric carcinoma and the relationship between clinicopathological features and we push the relationship between the high expression of mannose receptor and the clinicopathological features of gastric cancer. The mannose receptor may promote the growth, proliferation, and invasion of gastric cancer cells, and the malignancy is positively correlated with the expression of mannose receptor. The survival time of mannose receptor high expression patients is shorter than those with mannose receptor low expression. Multifactor regression analysis shows that the mannan receptor high table is an independent prognosis. The influence factors may be a potential tumor marker for poor prognosis in gastric cancer.2.. We found the high expression of miR-1260b in the colorectal cancer tissues and lymph node metastases, and the analysis of the association with the clinicopathological features, which is statistically significant to lymph node metastasis and venous infiltration, which means that miR-1260b may promote the conclusion. The survival time of patients with early metastasis of rectal cancer with high expression of.MiR-1260b was shorter than that of low expression ones. The correlation between MI R-1260b and survival time was analyzed by single factor analysis of COX regression, and multifactor analysis showed that high expression of miR-1260b was an independent influencing factor of poor prognosis and could be used as a potential tumor with poor prognosis. Sign.
【学位授予单位】：兰州大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R735

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