胰岛素样生长因子受体-1与cezanne-1在肺腺癌中的预后作用分析
发布时间：2018-12-23 10:11
【摘要】：研究背景及目的:肺癌是全球范围内发病率及死亡率最高的恶性肿瘤之一,在我国肺癌发病率和死亡率亦居各类癌症之首。据新的统计结果显示2012年全球肺癌新增病例数占癌症新发病例的13%。积极探索其发生发展机制、寻找潜在治疗靶点有助于肺癌的预防、早期诊断和疗效改善。研究表明,胰岛素样生长因子受体-1(Insulin-like Growth Factor-1 Receptor,IGF1R)信号通路在肿瘤的发生发展中发挥着重要作用。配体受体结合可引起IGF1R磷酸化并激活下游MAPK及PI3K等通路并影响肿瘤细胞增殖,分化,凋亡等。而其泛素化修饰及受体内吞在信号终止中其重要作用。Cezanne-1是近年来新发现的一种去泛素化酶,其与卵巢肿瘤蛋白酶(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与细胞周期和增殖密切相关且可参与表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)的去泛素化过程。本研究目的在于讨论IGF1R与cezanne-1的表达是否是肺腺癌患者的独立预后指标并讨论其相关性,进一步探讨cezanne-1作为IGF1R去泛素化酶的可能性。研究方法:在本研究中应用基因芯片数据库R2数据库进行IGF1R与cezanne-1表达情况之间的关系研究。另外,本研究还收集了 103例自2006年4月至2011年11月在山东大学附属省立医院进行根治性手术治疗的肺腺癌病例,所有病例均经病理确诊。在进行手术后,对病人进行五年以上的随访。收集临床信息及随访信息并对所取组织进行免疫组织化学染色,从而检测肿瘤中IGF1R与cezanne-1的表达。本研究中cezanne-1与IGF1R表达情况与病患临床病理特征的相关性采用Pearson卡法检验进行。并应用Cox比例风险模型进行多因素分析,从而寻找影响预后的独立临床因素。应用Kaplan-Meier法进行生存分析,并用Log-rank法比较不同组间存在的生存差异。通过卡法检验分析cezanne-1与IGF1R表达情况之间是否相关。研究结果:R2系统分析显示非小细胞肺癌患者肿瘤组织IGF1R高表达与不良预后相关。且非小细胞肺癌患者肿瘤组织中IGF1R与cezanne-1表达水平均较正常组织高,此外cezanne-1与IGF1R表达水平明显相关。在IGF1R和cezanne-1表达情况与临床病理资料相关性分析中,阳性表达的cezanne-1与淋巴结转移情况及病理分期相关(p=0.004,p=0.040)。单变量生存分析中,总生存期分别与cezanne-1表达(风险比HR=6.024,p0.001),IGF1R表达(风险比3.616,p=0.001),淋巴结转移(风险比3.059,p=0.001),肿瘤大小(风险比2.774,p=0.002)和分化程度(风险比7.430,p=0.006)相关。多变量Cox回归分析中,IGF1R和cezanne-1均是肺腺癌病人总生存期的独立危险因素。且 cezanne-1 与 IGF1R 表达情况密切相关(x 2=20.063,p0.001)。研究结论:本研究显示cezanne-1和IGF1R均为肺腺癌总生存期的独立危险因素,另外cezanne-1的表达情况与IGF1R表达情况呈现正相关,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.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2
本文编号：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.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2
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相关期刊论文 前2条
1 董强刚;黄进肃;黄建;卢丽琴;杨立民;;肺癌靶向治疗研究进展与我国肺癌的EGFR基因突变概况[J];肿瘤;2005年06期
2 陆舜;非小细胞肺癌综合治疗新进展[J];中国肺癌杂志;2005年01期
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