【摘要】：目的:RGS2的表達改變參與了許多惡性腫瘤的發(fā)生與發(fā)展。但是,RGS2表達改變與乳腺非特殊類型浸潤性癌之間的關系卻不是很清楚。因此,本研究將探討乳腺非特殊類型浸潤性癌中RGS2表達情況及其與臨床病理特征之間的關系,從而試圖探尋一個判斷乳腺癌患者預后及臨床診斷相關的新指標。方法:1.篩選出2011年重慶醫(yī)科大學分子檢測中心中196例BIC-NST標本,應用免疫組化的方法,檢測所有篩選出的BIC-NST標本中RGS2蛋白的表達量及分布情況,并將其與一些臨床病理參數(shù)的相關性進行分析。2.應用數(shù)據(jù)挖掘的方法,在TCGA數(shù)據(jù)庫中篩選出513例BIC-NST數(shù)據(jù),并分析其RGS2 m RNA的表達情況與臨床病理參數(shù)之間相關性。3.應用基因富集分析的方法,對TCGA數(shù)據(jù)庫中篩選出的513例乳腺癌數(shù)據(jù)進行生物學功能分析。結果:1.與正常乳腺組織相比,RGS2的m RNA和蛋白表達水平在BIC-NST中都明顯降低,且具有顯著統(tǒng)計學差異(P0.001)2.低表達的RGS2蛋白水平與較差的組織學分化(P=0.006),ER陽性表達(P=0.003),PR陽性表達(P=0.024),大于2cm的腫瘤體積(P=0.002)具有相關性。3.RGS2基因的低表達水平與較大的年齡(P=0.006),ER陽性表達(P0.001),PR陰性表達(P0.001),淋巴結的陽性轉移情況(P=0.011),TNM分期(P=0.020)具有相關性。4.RGS2的低表達水平與BIC-NST患者差預后相關(蛋白水平P=0.019,基因水平P=0.002),且可以成為BIC-NST患者預后不良的獨立因素(蛋白水平HR=4.602,95%CI=1.467-14.432,P=0.009;基因水平HR=2.299,95%CI=1.036-5.099,P=0.041)。5.通過基因富集分析發(fā)現(xiàn),RGS2 m RNA水平的低表達與乳腺癌雌激素α受體上調基因組(nominal P value=0.002,false discovery rate q value=0.1435)和luminal B型乳腺癌基因組(nominal P value=0.0,false discovery rate q value=0.1295)相關,RGS2 m RNA水平的高表達與細胞增殖負調控(nominal P value=0.0,false discovery rate q value=0.2224)和生長進程負調控(nominal P value=0.0,false discovery rate q value=0.2326)相關結論:首先,本研究的一系列結果提示RGS2可能與BIC-NST的抑癌基因相關,并且RGS2可能成為臨床判斷BIC-NST患者預后和輔助臨床病理診斷的有用指標。最后,本研究的流程方案很有可能成為今后大數(shù)據(jù)回顧性研究的研究趨勢。
[Abstract]:Objective the change of RGS2 expression is involved in the occurrence and development of many malignant tumors. However, the relationship between changes in RGS2 expression and non-specific types of invasive breast cancer is not clear. Therefore, this study will explore the expression of RGS2 and its relationship with clinicopathological features in non-special types of breast cancer, in order to explore a new indicator for the prognosis and clinical diagnosis of breast cancer. Method 1: 1. 196 BIC-NST samples from molecular detection center of Chongqing Medical University in 2011 were screened. The expression and distribution of RGS2 protein in all selected BIC-NST samples were detected by immunohistochemical method. The correlation between it and some clinicopathological parameters was analyzed. 2. 2. 513 BIC-NST data were screened from TCGA database by data mining, and the correlation between RGS2 mRNA expression and clinicopathological parameters was analyzed. The biological function of 513 breast cancer data selected from TCGA database was analyzed by gene enrichment analysis. The result is 1: 1. The mRNA and protein expression of RGS2 in BIC-NST was significantly lower than that in normal breast tissues (P0.001). The low expression level of RGS2 protein and the poor histological differentiation (P0. 006) of ER positive expression (P0. 003) positive expression of PR (P0. 024), larger than the tumor volume of 2cm (P0. 002) have a correlation. 3. The low expression level of RGS2 gene and the age (P0. 006) of ER positive expression (P0. 001) PR negative expression (P0. 001), lymphocytic cell negative expression (P0. 001). The low expression level of RGS2 was correlated with the poor prognosis of BIC-NST patients (protein level P0. 019, gene level P0. 002), and could be an independent factor of poor prognosis in BIC-NST patients (protein level HR4. 602 ~ 95CII 1.467-14. 432P0. 009; gene level HR2. 299 / 95CII 1.036-5.099P0.041). By gene enrichment analysis, it was found that the low expression of RGS2 mRNA was associated with the high expression of RGS2 mRNA in breast cancer associated with estrogen 偽 receptor up-regulated discovery rate q value=0.1435 (nominal P value0. 002 false discovery rate q value=0.1435) and luminal B breast cancer genome (nominal P value0. 0false discovery rate q value=0.1295). Conclusions: nominal P value0. 0. 0. 0. 0. 0. 0. Discovery rate q value=0.2326 discovery rate q value=0.2224 and nominal P value 0. 0. 0. 0. 0 discovery rate q value=0.2326. A series of results suggest that RGS2 may be associated with the tumor suppressor gene of BIC-NST, and RGS2 may be a useful marker for clinical prognosis and clinicopathologic diagnosis of BIC-NST patients. Finally, the flow scheme of this study is likely to be the research trend of big data retrospective research in the future.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R737.9

【參考文獻】

相關期刊論文 前1條

1 ;Chromosomal aberrations related to metastasis of human solid tumors[J];World Journal of Gastroenterology;2002年05期

，

本文編號：2130122