胰島素樣生長因子受體-1與cezanne-1在肺腺癌中的預后作用分析
發(fā)布時間：2018-12-23 10:11
【摘要】：研究背景及目的:肺癌是全球范圍內(nèi)發(fā)病率及死亡率最高的惡性腫瘤之一,在我國肺癌發(fā)病率和死亡率亦居各類癌癥之首。據(jù)新的統(tǒng)計結(jié)果顯示2012年全球肺癌新增病例數(shù)占癌癥新發(fā)病例的13%。積極探索其發(fā)生發(fā)展機制、尋找潛在治療靶點有助于肺癌的預防、早期診斷和療效改善。研究表明,胰島素樣生長因子受體-1(Insulin-like Growth Factor-1 Receptor,IGF1R)信號通路在腫瘤的發(fā)生發(fā)展中發(fā)揮著重要作用。配體受體結(jié)合可引起IGF1R磷酸化并激活下游MAPK及PI3K等通路并影響腫瘤細胞增殖,分化,凋亡等。而其泛素化修飾及受體內(nèi)吞在信號終止中其重要作用。Cezanne-1是近年來新發(fā)現(xiàn)的一種去泛素化酶,其與卵巢腫瘤蛋白酶(Ovarian Tumor Proteases,OTUs)家族下的A20去泛素化酶具有一定的相似性。研究表明cezanne-1與細胞周期和增殖密切相關且可參與表皮生長因子受體(Epidermal Growth Factor Receptor,EGFR)的去泛素化過程。本研究目的在于討論IGF1R與cezanne-1的表達是否是肺腺癌患者的獨立預后指標并討論其相關性,進一步探討cezanne-1作為IGF1R去泛素化酶的可能性。研究方法:在本研究中應用基因芯片數(shù)據(jù)庫R2數(shù)據(jù)庫進行IGF1R與cezanne-1表達情況之間的關系研究。另外,本研究還收集了 103例自2006年4月至2011年11月在山東大學附屬省立醫(yī)院進行根治性手術治療的肺腺癌病例,所有病例均經(jīng)病理確診。在進行手術后,對病人進行五年以上的隨訪。收集臨床信息及隨訪信息并對所取組織進行免疫組織化學染色,從而檢測腫瘤中IGF1R與cezanne-1的表達。本研究中cezanne-1與IGF1R表達情況與病患臨床病理特征的相關性采用Pearson卡法檢驗進行。并應用Cox比例風險模型進行多因素分析,從而尋找影響預后的獨立臨床因素。應用Kaplan-Meier法進行生存分析,并用Log-rank法比較不同組間存在的生存差異。通過卡法檢驗分析cezanne-1與IGF1R表達情況之間是否相關。研究結(jié)果:R2系統(tǒng)分析顯示非小細胞肺癌患者腫瘤組織IGF1R高表達與不良預后相關。且非小細胞肺癌患者腫瘤組織中IGF1R與cezanne-1表達水平均較正常組織高,此外cezanne-1與IGF1R表達水平明顯相關。在IGF1R和cezanne-1表達情況與臨床病理資料相關性分析中,陽性表達的cezanne-1與淋巴結(jié)轉(zhuǎn)移情況及病理分期相關(p=0.004,p=0.040)。單變量生存分析中,總生存期分別與cezanne-1表達(風險比HR=6.024,p0.001),IGF1R表達(風險比3.616,p=0.001),淋巴結(jié)轉(zhuǎn)移(風險比3.059,p=0.001),腫瘤大小(風險比2.774,p=0.002)和分化程度(風險比7.430,p=0.006)相關。多變量Cox回歸分析中,IGF1R和cezanne-1均是肺腺癌病人總生存期的獨立危險因素。且 cezanne-1 與 IGF1R 表達情況密切相關(x 2=20.063,p0.001)。研究結(jié)論:本研究顯示cezanne-1和IGF1R均為肺腺癌總生存期的獨立危險因素,另外cezanne-1的表達情況與IGF1R表達情況呈現(xiàn)正相關,提示cezanne-1可能是IGF1R的去泛素化酶。
[Abstract]:Background and objective: lung cancer is one of the highest morbidity and mortality in the world. New statistics show that new cases of lung cancer accounted for 13 new cases worldwide in 2012. To explore the mechanism of its occurrence and development and to find potential therapeutic targets are helpful to the prevention, early diagnosis and improvement of curative effect of lung cancer. It has been shown that insulin-like growth factor receptor-1 (Insulin-like Growth Factor-1 Receptor,IGF1R) signaling pathway plays an important role in tumorigenesis and development. Ligand receptor binding can induce IGF1R phosphorylation, activate downstream MAPK and PI3K pathways and affect tumor cell proliferation, differentiation and apoptosis. However, Ubiquitin modification and ingestion in vivo play an important role in signal termination. Cezanne-1 is a newly discovered diubiquitin enzyme, which is associated with ovarian tumor protease (Ovarian Tumor Proteases,. OTUs) family A 20 desuginase has a certain similarity. It has been shown that cezanne-1 is closely related to cell cycle and proliferation and may be involved in the deubiquification of epidermal growth factor receptor (Epidermal Growth Factor Receptor,EGFR). The purpose of this study was to investigate whether the expression of IGF1R and cezanne-1 was an independent prognostic marker in patients with lung adenocarcinoma, and to explore the possibility of cezanne-1 as a IGF1R diubiquitin enzyme. Methods: in this study, the gene chip database R2 was used to study the relationship between IGF1R and cezanne-1 expression. In addition 103 cases of lung adenocarcinoma treated with radical surgery from April 2006 to November 2011 were collected. All cases were confirmed by pathology. Patients were followed up for more than five years after the operation. The expression of IGF1R and cezanne-1 in tumor was detected by collecting clinical information and follow-up information and immunohistochemical staining. The correlation between the expression of cezanne-1 and IGF1R and the clinicopathological features of the patients was examined by Pearson card test. Cox proportional risk model was used for multivariate analysis to find independent clinical factors affecting prognosis. Kaplan-Meier method was used to analyze survival and Log-rank method was used to compare the survival differences among different groups. The correlation between cezanne-1 and IGF1R expression was analyzed by card test. Results: R2 system analysis showed that high expression of IGF1R was associated with poor prognosis in patients with NSCLC. The expression levels of IGF1R and cezanne-1 in NSCLC patients were higher than those in normal tissues, and the expression of cezanne-1 and IGF1R were significantly correlated. In the correlation analysis between the expression of IGF1R and cezanne-1 and the clinicopathological data, the positive expression of cezanne-1 was correlated with lymph node metastasis and pathological stage (p0. 004 / p0. 040). In univariate survival analysis, the total survival time was correlated with the expression of cezanne-1 (risk ratio HR=6.024,p0.001), IGF1R expression (risk ratio 3.616%, p0 001), lymph node metastasis (risk ratio 3.059%, p0 001). Tumor size (risk ratio: 2.774) was correlated with differentiation (risk ratio: 7.430%, p0.006). In multivariate Cox regression analysis, IGF1R and cezanne-1 were independent risk factors for total survival of patients with lung adenocarcinoma. The expression of cezanne-1 was closely related to the expression of IGF1R (x 2 0. 063 P 0. 001). Conclusion: both cezanne-1 and IGF1R are independent risk factors for the total survival time of lung adenocarcinoma, and the expression of cezanne-1 is positively correlated with the expression of IGF1R, suggesting that cezanne-1 may be the IGF1R deoxyuridine enzyme.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R734.2
本文編號：2389828
[Abstract]:Background and objective: lung cancer is one of the highest morbidity and mortality in the world. New statistics show that new cases of lung cancer accounted for 13 new cases worldwide in 2012. To explore the mechanism of its occurrence and development and to find potential therapeutic targets are helpful to the prevention, early diagnosis and improvement of curative effect of lung cancer. It has been shown that insulin-like growth factor receptor-1 (Insulin-like Growth Factor-1 Receptor,IGF1R) signaling pathway plays an important role in tumorigenesis and development. Ligand receptor binding can induce IGF1R phosphorylation, activate downstream MAPK and PI3K pathways and affect tumor cell proliferation, differentiation and apoptosis. However, Ubiquitin modification and ingestion in vivo play an important role in signal termination. Cezanne-1 is a newly discovered diubiquitin enzyme, which is associated with ovarian tumor protease (Ovarian Tumor Proteases,. OTUs) family A 20 desuginase has a certain similarity. It has been shown that cezanne-1 is closely related to cell cycle and proliferation and may be involved in the deubiquification of epidermal growth factor receptor (Epidermal Growth Factor Receptor,EGFR). The purpose of this study was to investigate whether the expression of IGF1R and cezanne-1 was an independent prognostic marker in patients with lung adenocarcinoma, and to explore the possibility of cezanne-1 as a IGF1R diubiquitin enzyme. Methods: in this study, the gene chip database R2 was used to study the relationship between IGF1R and cezanne-1 expression. In addition 103 cases of lung adenocarcinoma treated with radical surgery from April 2006 to November 2011 were collected. All cases were confirmed by pathology. Patients were followed up for more than five years after the operation. The expression of IGF1R and cezanne-1 in tumor was detected by collecting clinical information and follow-up information and immunohistochemical staining. The correlation between the expression of cezanne-1 and IGF1R and the clinicopathological features of the patients was examined by Pearson card test. Cox proportional risk model was used for multivariate analysis to find independent clinical factors affecting prognosis. Kaplan-Meier method was used to analyze survival and Log-rank method was used to compare the survival differences among different groups. The correlation between cezanne-1 and IGF1R expression was analyzed by card test. Results: R2 system analysis showed that high expression of IGF1R was associated with poor prognosis in patients with NSCLC. The expression levels of IGF1R and cezanne-1 in NSCLC patients were higher than those in normal tissues, and the expression of cezanne-1 and IGF1R were significantly correlated. In the correlation analysis between the expression of IGF1R and cezanne-1 and the clinicopathological data, the positive expression of cezanne-1 was correlated with lymph node metastasis and pathological stage (p0. 004 / p0. 040). In univariate survival analysis, the total survival time was correlated with the expression of cezanne-1 (risk ratio HR=6.024,p0.001), IGF1R expression (risk ratio 3.616%, p0 001), lymph node metastasis (risk ratio 3.059%, p0 001). Tumor size (risk ratio: 2.774) was correlated with differentiation (risk ratio: 7.430%, p0.006). In multivariate Cox regression analysis, IGF1R and cezanne-1 were independent risk factors for total survival of patients with lung adenocarcinoma. The expression of cezanne-1 was closely related to the expression of IGF1R (x 2 0. 063 P 0. 001). Conclusion: both cezanne-1 and IGF1R are independent risk factors for the total survival time of lung adenocarcinoma, and the expression of cezanne-1 is positively correlated with the expression of IGF1R, suggesting that cezanne-1 may be the IGF1R deoxyuridine enzyme.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R734.2
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相關期刊論文 前2條
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