miR-195、Cdc42在食管癌组织中的表达与预后的相关性分析

发布时间：2018-03-31 00:39

本文选题：食管鳞状细胞癌　切入点：微小RNA-195　出处：《新乡医学院》2015年硕士论文

【摘要】：背景食管癌是常见的消化系统恶性肿瘤,发病率高,5年生存率低,仅15%左右,河南省安阳林州及周边地区是中国也是世界食管癌发病率最高的地区。在临床工作中,确定食管癌的临床结局主要参考临床病理特征,如TNM分期等。但是在大规模流行病调查工作中发现TNM分期并不能准确的预测患者的预后,所以寻找能够预测食管癌预后的生物标志物具有重要意义。细胞分裂周期蛋白42(Cell division cycle protein 42,Cdc42)是微小RNA-195 (MicroRNA-195,miR-195)的靶基因,研究发现miR-195、 Cdc42可能参与了食管癌的发生过程,但在人类食管癌组织中的表达及其临床意义尚不清楚。目的探讨miR-195、Cdc42在食管癌组织中的表达与预后的相关性,旨在探讨二者作为食管癌预后评价生物标志物的可能性。方法1.研究对象：571例行根治切除手术的原发性食管癌患者均来自河南省豫北地区某三级甲等医院,患者临床病理资料完整、术中病理标本保存完好者,通过随访明确患者术后生存时间(随访时间截止到2013年12月)。随访期间所进行的检查包括食管造影,CT扫描及骨扫描等以及时发现复发和或转移。随访间隔时间第1年每3个月1次,第2年每6个月1次。随机抽取98例作为研究对象。2.实验方法：入选患者术中病理组织标本(既往收集的术中新鲜病理组织标本冷冻保存于_80℃冰箱中),HE染色确定组织病理类型；应用Taqman荧光定量PCR(qRT-PCR)法检测miR-195和Cdc42在食管癌组织、癌旁组织及正常食管组织中的表达。运用χ2检验分析miR-195、Cdc42的表达与临床病理特征的关系,运用Kaplan-Meier生存分析、Cox比例风险模型等进行预后分析。结果1.HE染色结果显示：98例为食管鳞状细胞癌；98例为食管癌旁组织；10例为正常食管组织。2. qRT-PCR检测结果显示：miR-195在食管癌组织中相对表达含量与癌旁组织和正常食管组织比较显著下调(P0.001)；Cdc42在食管癌组织中相对表达含量与癌旁组织和正常食管组织比较显著上调(P0.001)；Spearman相关分析显示：miR-195和Cdc42的表达水平呈负相关(P0.001)。3.miR-195的低表达与TNM分期和淋巴结转移显著相关(P0.05)；Cdc42的高表达与TNM分期和肿瘤分化程度显著相关(P0.05)。4. Kaplan-Meier生存分析显示：Low-miR-195组或High-Cdc42组患者的总生存期(OS)和无进展生存期(PFS)短于High-miR-195组或Low-Cdc42组(P0.001)；Low-miR-195/High-Cdc42同时表达时OS和PFS较短,按照OS和PFS从长到短依次为High-miR-195/Low-Cdc42、High-miR-195/High-Cdc42、Low-miR-195 /Low-Cdc42、Low-miR-195/High-Cdc42。5.Cox比例风险模型多因素分析显示：TNM分期、肿瘤分化、淋巴结转移、Low-miR-195、High-Cdc42或Low-miR-195/High-Cdc42同时表达等是影响食管癌患者OS和PFS的独立危险因素(P0.05)。结论食管癌组织中miR-195表达下调、Cdc42表达上调、Low-miR-195/High-Cdc42同时表达等均提示预后不良,是食管癌患者预后不良的独立危险因素。miR-195、Cdc42可作为食管癌预后评价的生物标志物。
[Abstract]:Background: esophageal cancer is the common malignant tumor of digestive system, high incidence rate, 5 year survival rate is low, only about 15%, Henan Province, Anyang, Linzhou and the surrounding area is also China esophageal cancer in the world. The highest rate in the clinical work, the main parameters determining outcome of esophageal cancer clinical pathological features, such as TNM stage. But find prognostic staging in patients with TNM was not accurate in large-scale epidemiological survey work, so the search for biomarkers to predict the prognosis of esophageal cancer has important significance. The cell cycle protein 42 (Cell division cycle protein 42, Cdc42) is a small RNA-195 (MicroRNA-195, miR-195) of the target gene, research the discovery of miR-195, Cdc42 may participate in the process of esophageal cancer, but the expression in human esophageal carcinoma and its clinical significance is unclear. Objective to investigate the effect of miR-195, Cdc42 in esophageal cancer group The relationship between the expression and prognosis in fabric, aims to explore the two as the prognosis of esophageal cancer biomarker evaluation possibilities. Methods 1. subjects: 571 cases underwent radical resection of primary esophageal cancer patients from the northern area of Henan Province, a three grade hospital, clinical pathological data were complete, well preserved pathology specimens during the operation, the survival time of the patients with postoperative follow-up clear (follow-up until December 2013). The follow-up examination included esophageal radiography, CT scan and bone scan and found recurrence and / or metastasis. The follow-up interval of first years every 3 months for 1 times, second years every 6 months for 1 times. 98 patients were randomly selected as the research object.2. methods: selected patients with pathological tissue specimens (previously collected in the operation of fresh tissue cryopreservation at _80 deg.c in the refrigerator), HE staining to determine the tissue pathological types ; application of Taqman fluorescence quantitative PCR (qRT-PCR) was used to detect miR-195 and Cdc42 expression in esophageal cancer tissue, adjacent tissues and normal esophageal tissues. Using 2 test analysis of miR-195, the relationship between Cdc42 expression and clinicopathological features, prognosis by Kaplan-Meier survival analysis, Cox proportional hazards regression model. The results of 1.HE staining results: 98 cases of esophageal squamous cell carcinoma; 98 cases of esophageal cancer; 10 cases of normal esophageal tissue.2. qRT-PCR test results show that: miR-195 in esophageal carcinoma and the relative expression content in adjacent tissues and normal esophageal tissue significantly decreased (P0.001); Cdc42 in human esophageal carcinoma tissues, the relative expression content with the adjacent tissues and normal esophageal tissue increased significantly (P0.001); Spearman correlation analysis showed that the expression level of miR-195 was negatively related to Cdc42 and the low expression of.3.miR-195 (P0.001) With TNM staging and lymph node metastasis was significantly correlated (P0.05); and the high expression of TNM was significantly related to Cdc42 staging and tumor differentiation (P0.05).4. Kaplan-Meier survival analysis showed that overall survival in Low-miR-195 group or High-Cdc42 group (OS) and progression free survival (PFS) was shorter than that of group High-miR-195 or group Low-Cdc42 (P0.001; Low-miR-195/High-Cdc42) expression of OS and PFS at the same time is short, according to OS and PFS from long to short sequence of High-miR-195/Low-Cdc42, High-miR-195/High-Cdc42, Low-miR-195, /Low-Cdc42, multivariate Low-miR-195/High-Cdc42.5.Cox proportional risk model analysis showed that TNM stage, tumor differentiation, lymph node metastasis, Low-miR-195, High-Cdc42 or Low-miR-195/High-Cdc42 at the same time, the expression is independent risk and OS PFS factors in patients with esophageal cancer (P0.05). Conclusion the expression of miR-195 in esophageal cancer tissues, Cdc42 expression, Low-miR-195/ High-Cdc42 expression at the same time indicates poor prognosis. It is an independent risk factor for poor prognosis of esophageal cancer..miR-195 and Cdc42 can be used as biomarkers for prognosis evaluation of esophageal cancer.

【学位授予单位】：新乡医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.1

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