非小细胞肺癌中卵巢肿瘤结构域蛋白酶1的表达及其临床意义

发布时间：2018-05-29 14:07

本文选题：卵巢肿瘤结构域蛋白酶1 + 非小细胞肺癌　；参考：《山东大学》2017年硕士论文

【摘要】：背景和目的:在全世界范围内肺癌的发病率排名第一,每一年大约有140万至160万人因为肺癌而死亡,近几年来,肺癌的发病率和死亡率正在迅速增加,肺癌的发生和发展受有多种因素,吸烟、电离辐射、肺部的慢性感染史以及环境污染使得肺癌发病率成为我国恶性肿瘤发病率首位。绝大多数的肺癌起源于支气管粘膜上皮,所以肺癌也称为支气管肺癌,肺癌的常见病理类型为非小细胞肺癌和小细胞肺癌,其中非小细胞肺癌又包括鳞状细胞癌、腺癌以及大细胞肺癌,在肺癌的所有病例中非小细胞肺癌大约能占到85%,虽然在过去几十年里,外科手术技术在不断的改善,放化疗不断进展以及新型分子靶向药物的出现,但遗憾的是肺癌的总体5年生存率依旧不高,大约为17.1%。作为细胞内蛋白质主要降解途径的泛素-蛋白酶体系统(UPS),在很多病理及其生理的过程中起到关键作用,包括细胞周期调控,细胞凋亡,炎症,信号转导等。泛素-蛋白酶体系统是一个可逆过程,去泛素化酶(Deubiquitinating enzymes,DUBs)对该过程有着调节作用,研究表明,DUBs参与细胞生长和凋亡,在遗传性肿瘤、神经变性疾病等也发挥了重要作用。卵巢肿瘤结构域蛋白酶(OTUs)是去泛素化酶家族主要成员之一,其中卵巢肿瘤结构域蛋白酶 1(Ovarian tumor domain-containing protease 1,OTUD1)蛋白广泛表达于人类的很多组织内,如肾、肠、脑、肝、肺等。本次实验检测了 OTUD1基因在非小细胞肺癌(NSCLC)组织及癌旁组织中的表达情况,进步来探究OTUD1的表达与其临床意义。研究方法:选取2008年3月至2009年2月在山东大学齐鲁医院胸外科行手术治疗的82例非小细胞肺癌患者组织标本,同时选取40例正常肺组织标本作为阴性对照,采用免疫组化法检测OTUD1在肺癌组织及癌旁组织中的表达情况;另取2015年3月至2015年4月在山东大学齐鲁医院胸外科手术治疗的原发性非小细胞肺癌25例,应用Real-time PCR检测OUT1在非小细胞肺癌组织及邻近正常肺组织内的表达情况。整理82例患者临床相关病理因素及随访资料,采用SPSS 19.0统计软件对数据进行分析,两组间率的比较采用χ2检验,采用Kaplan-Meier法和Log-rank检验分析生存期差异,Cox回归多因素分析判定独立预后影响因素。结果:免疫组化检测非小细胞肺癌组织及癌旁组织组织中OTUD1的mRNA的表达率分别为48.7%(40/82)和12.5%(5/40),两者有统计学差异(P0.01);OTUD1的表达与患者的年龄(P=0.386)、性别(P=0.392)、吸烟史(P=0.632)、病理类型(P=0.801)均无显著相关性;与淋巴结转移(P=0.005)、分化程度(P=0.006)及TNM分期(P =0.015)显著相关。通过单因素和多因素的分析得出,患者的不良预后与淋巴结转移、TNM分期、OTUD1高表达相关,均P0.01。结论:非小细胞肺癌组织中OTUD1高表达,OTUD1的高表达与非小细胞肺癌的恶性进展及不良预后息息相关,因此OTUD1可以作为判断非小细胞肺癌生物学特征及预后的参考指标。
[Abstract]:Background and objective: lung cancer is the highest incidence rate in the world, with about 1.4 million to 1.6 million people dying from lung cancer every year. In recent years, lung cancer morbidity and mortality are increasing rapidly. The occurrence and development of lung cancer are affected by many factors, such as smoking, ionizing radiation, history of chronic lung infection and environmental pollution, which make the incidence of lung cancer the first in China. The vast majority of lung cancer originated from the bronchial mucosa epithelium, so lung cancer is also known as bronchial lung cancer. The common pathological types of lung cancer are non-small cell lung cancer and small cell lung cancer, in which non-small cell lung cancer also includes squamous cell carcinoma. Adenocarcinoma and large cell lung cancer account for about 85 percent of all cases of non-small cell lung cancer, although surgical techniques have improved over the past few decades, advances in radiotherapy and chemotherapy, and the emergence of new molecular targeting drugs. Unfortunately, the overall 5-year survival rate for lung cancer is still low, about 17. 1%. The ubiquitin proteasome system, which is the main pathway of protein degradation in cells, plays a key role in many pathological and physiological processes, including cell cycle regulation, apoptosis, inflammation, signal transduction and so on. The ubiquitin proteasome system is a reversible process, which is regulated by the deubiquitin deoxyribonucleic acid (DUBs). It has been shown that DUBs are involved in cell growth and apoptosis, and play an important role in hereditary tumors, neurodegenerative diseases and so on. Ovarian tumor domain protease (OTUS) is one of the major members of the diubiquitin enzyme family. The protein of ovarian tumor domain protease 1(Ovarian tumor domain-containing protease 1 / OTUD1 is widely expressed in many human tissues, such as kidney, intestine, brain, liver, lung and so on. In this study, we examined the expression of OTUD1 gene in non-small cell lung cancer (NSCLC) tissues and adjacent tissues to explore the expression of OTUD1 and its clinical significance. Methods: from March 2008 to February 2009, 82 cases of non-small cell lung cancer (NSCLC) were collected from thoracic surgery department of Qilu Hospital, Shandong University, and 40 cases of normal lung tissue were selected as negative control. Immunohistochemical method was used to detect the expression of OTUD1 in lung cancer tissues and adjacent tissues, and 25 cases of primary non-small cell lung cancer (NSCLC) treated by thoracic surgery in Qilu Hospital of Shandong University from March 2015 to April 2015 were selected. Real-time PCR was used to detect the expression of OUT1 in non-small cell lung cancer (NSCLC) and adjacent normal lung tissues. The clinicopathological factors and follow-up data of 82 patients were analyzed by SPSS 19.0 statistical software. The rate of the two groups was compared by 蠂 2 test. Kaplan-Meier method and Log-rank test were used to analyze the difference of survival time and multivariate analysis was used to determine the independent prognostic factors. Results: the expression rates of OTUD1 mRNA in non-small cell lung cancer (NSCLC) tissues and adjacent tissues were 48.7 / 82 and 12.5 / 40 respectively. There was no significant correlation between the expression of OTUD1 and age, sex P0.3922, smoking history P0.632and pathological type P 0.801. There was a significant correlation between P0. 005, P0. 006) and TNM staging (P 0. 015). Univariate and multivariate analysis showed that the poor prognosis was correlated with the high expression of OTUD1 in TNM stage of lymph node metastasis (all P 0.01). Conclusion: the high expression of OTUD1 in non-small cell lung cancer is closely related to the malignant progression and poor prognosis of non-small cell lung cancer. Therefore, OTUD1 can be used as a reference index to judge the biological characteristics and prognosis of non-small cell lung cancer.
【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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