本文選題：胃癌 + 甘露糖受體��； 參考：《蘭州大學(xué)》2017年博士論文

【摘要】：目的:1.第一部分通過對120例胃癌手術(shù)患者的臨床資料進(jìn)行整理,研究甘露糖受體(MR)在胃癌組織中的表達(dá)及與臨床特征之間的關(guān)系,進(jìn)一步分析其與胃癌患者生存時間之間的關(guān)系,評價其在臨床預(yù)后中的價值。2.第二部分研究120例CRC患者miR-1260b表達(dá)及與臨床病理特征的關(guān)系,分析miR-1260b與結(jié)腸癌患者生存時間之間關(guān)系,評價其在臨床預(yù)后中的價值。方法:1.分別對120例胃癌患者的癌組織及相應(yīng)癌旁組織使用免疫組織化學(xué)及RT-PCR分析法測定甘露糖受體的表達(dá)。根據(jù)染色強(qiáng)度得分將患者分為甘露糖受體低表達(dá)組與甘露糖受體高表達(dá)組。采用卡方檢驗分析甘露糖受體的表達(dá)與臨床病理特征之間的關(guān)系。Kaplan-Meier法(基于甘露糖受體表達(dá)數(shù)據(jù))繪制生存曲線,兩組間的生存期差異采用Log-rank檢驗比較�？偵嫫�(OS)和無病生存期(DFS)為主要結(jié)果。并通過單因素及多因素COX回歸模型分析甘露糖受體的表達(dá)與生存時間的的關(guān)系。對收集的120對CRC組織樣本,采用Real-time PCR檢測miR-1260b的表達(dá)。根據(jù)中間值分為二組,分析CRC組織中miR-1260b高表達(dá)與臨床病理特征之間的關(guān)系。生存分析采用Kaplan-Meier法繪制生存曲線,兩組間的生存期的差異log-rank檢驗比較。并通過單因素及多因素COX回歸模型分析miR-1260b的表達(dá)與生存時間的關(guān)系。結(jié)果:第一部分甘露糖受體在胃癌中預(yù)后價值的研究1.胃癌組織中甘露糖受體的表達(dá),根據(jù)染色強(qiáng)度得分把患者分為兩組:甘露糖受體低表達(dá)組與甘露糖受體高表達(dá)組。甘露糖受體蛋白在胃癌細(xì)胞中的表達(dá)率高達(dá)45.8%(54/120),顯著高于癌旁組織20%(36/120)(χ2=6.286,P=0.012)。為了進(jìn)一步驗證免疫組化結(jié)果,采用PT-PCR檢測甘露糖受體mRNA的表達(dá)水平。隨機(jī)選擇了30例患者,分別取胃癌組織及相應(yīng)癌旁組織。30對樣本中的19例顯示,與相應(yīng)癌旁組織相比,胃癌組織中的甘露糖受體mRNA表達(dá)增加2倍以上,最高增加14.7倍。2.胃癌組織中甘露糖受體與患者的臨床病理特征之間的關(guān)系甘露糖受體高表達(dá)與胃癌患者臨床病理特征中的腫瘤大小、T分期、N分期及UICC分期有統(tǒng)計學(xué)意義(P0.05)。而與胃癌患者的年齡、性別、M分期、腫瘤定位、Lauren分型、淋巴管浸潤,及術(shù)后化療與甘露糖受體表達(dá)沒有統(tǒng)計學(xué)意義(P0.05)。3.甘露糖受體表達(dá)與胃癌患者的預(yù)后Kaplan-Meier生存曲線表明,甘露糖受體高表達(dá)組患者的DFS與OS均明顯短于甘露糖受體低表達(dá)組患者(log-rank P0.05)。采用COX回歸模型,分析影響胃癌患者DFS和OS的每個變量。單因素分析結(jié)果提示胃癌患者預(yù)后與甘露糖受體表達(dá)水平密切相關(guān)。多因素分析結(jié)果表明:甘露糖受體的高表達(dá)是胃癌患者預(yù)后不良的獨立影響因素。第二部分miRNA-1260b在結(jié)直腸癌中預(yù)后價值的研究1.結(jié)直腸癌組織與正常組織miR-1260b表達(dá)及有、無淋巴結(jié)轉(zhuǎn)移患者結(jié)直腸癌組織miR-1260b表達(dá)水平CRC組織中mi R-1260b的表達(dá)顯著高于相應(yīng)癌旁組織中miR-1260b的表達(dá)水平(P0.001)。按淋巴結(jié)有、無轉(zhuǎn)移分兩組,分析不同淋巴結(jié)狀態(tài)患者miR-1260b表達(dá)水平。與無淋巴結(jié)轉(zhuǎn)移患者相比,發(fā)生淋巴結(jié)轉(zhuǎn)移的患者CRC組織miR-1260b表達(dá)水平有統(tǒng)計學(xué)意義(P0.001)。2.miR-1260b表達(dá)與臨床病理特征之間的關(guān)系根據(jù)mi R-1260b表達(dá)水平(2-ΔΔ中位數(shù)為中間值),將120例CRC患者分為miR-1260b高表達(dá)組與miR-1260b低表達(dá)組。即分為:67例高表達(dá)組CRC患者和53例低表達(dá)組CRC患者。分析CRC患者的臨床病理特征與miR-1260b表達(dá)之間的關(guān)系。我們發(fā)現(xiàn),高表達(dá)miR-1260b的CRC患者與淋巴結(jié)轉(zhuǎn)移(P0.05)及靜脈浸潤(P0.001)有統(tǒng)計學(xué)意義。而與其它的臨床參數(shù),如年齡、性別、腫瘤的大小、分化程度、浸潤的深度及腫瘤的位置無統(tǒng)計學(xué)意義(P0.05)。3.miR-1260b表達(dá)與CRC患者的預(yù)后我們采用Kaplan-Meier方法繪制所有患者生存曲線(DFS和OS)。結(jié)果表明,患者miR-1260b高表達(dá)的CRC生存時間明顯低于mi R-1260b低表達(dá)水平的CRC者。單因素分析顯示,靜脈浸潤(P0.05)、腫瘤浸潤深度、淋巴結(jié)轉(zhuǎn)移以及高miR-1260b表達(dá)水平(P0.01)與OS統(tǒng)計學(xué)意義。采用COX回歸模型進(jìn)行多因素分析,提示miR-1260b高表達(dá)預(yù)示著患者的預(yù)后不良。結(jié)論:1.通過甘露糖受體在胃癌組織中的高表達(dá)及臨床病理特征之間的關(guān)系,我們推測甘露糖受體可能促進(jìn)胃癌細(xì)胞的生長、增殖和侵襲,惡性程度與甘露糖受體的表達(dá)呈正相關(guān)。與甘露糖受體低表達(dá)的患者相比,甘露糖受體高表達(dá)患者的生存時間短。多因素回歸分析表明,甘露糖受體高表是患者預(yù)后不良的一個獨立影響因素,可能是胃癌患者預(yù)后不良的潛在腫瘤標(biāo)志物。2.我們發(fā)現(xiàn)結(jié)直腸中癌組織及淋巴結(jié)轉(zhuǎn)移患者miR-1260b高表達(dá),同時結(jié)合與臨床病理特征之間的關(guān)系分析,其與淋巴結(jié)轉(zhuǎn)移及靜脈浸潤有統(tǒng)計學(xué)意義,這意味著miR-1260b可能促進(jìn)了結(jié)直腸癌的早期轉(zhuǎn)移。miR-1260b高表達(dá)的患者的生存時間比低表達(dá)者短,采用COX回歸單因素分析mi R-1260b與生存時間之間有相關(guān)性,進(jìn)行多因素分析,表明miR-1260b高表達(dá)是患者預(yù)后不良的一個獨立影響因素,可作為患者預(yù)后不良的潛在腫瘤標(biāo)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.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R735

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