黏蛋白1在食管鳞癌中的表达及其与临床病理及预后的关系

发布时间：2018-01-22 06:15

本文关键词： 食管鳞癌 MUC1 临床病理预后　出处：《山东大学》2015年硕士论文　论文类型：学位论文

【摘要】：[背景与目的]食管癌的病理类型中鳞癌占90%以上且患者预后不佳。目前TNM分期是判断食管鳞癌患者预后的主要方法,但仍缺乏敏感性。故寻找准确的肿瘤分子生物学标志物判断食管鳞癌患者的预后对于指导临床治疗具有重要意义。多项研究发现黏蛋白1(MUC1)在多种肿瘤细胞中高表达,并与肿瘤的发生、发展、侵袭、转移、预后等密切相关。本研究通过检测MUC1在食管鳞癌和正常食管组织中的表达,分析其表达程度与临床病理及患者预后的关系。[方法]对2007年1月至2010年1月间接受手术治疗且临床病理资料完整的76例食管鳞癌患者进行回顾性研究。分别采用蛋白质免疫印迹法(Western-blotting)和免疫组织化学染色法(IHC)检测76例食管鳞癌组织和19例正常食管粘膜组织中MUC1的表达差异,并依据文献上的方法进行结果判定。应用SPSS19.0统计软件分析,建立数据库。采用X2检验判断相关性,采用Kaplan-Meier法进行生存分析,采用Log-rank检验判断生存差异性,采用Cox比例风险模型进行多因素分析判定独立预后因素。[结果]1、Western-blotting检测：MUCl在食管鳞癌组织及正常食管组织中的相对表达水平分别为0.77±0.11和0.24±0.89,差异明显,具有统计学意义(F=7.6,P0.05)。2、免疫组化检测：在食管鳞癌组织中MUC1的表达较正常食管组织中明显升高。MUC1在正常食管组织中仅在细胞膜及部分细胞核微弱表达,而在食管鳞癌组织中MUC1以细胞核表达为主,部分表达于细胞膜,这与MUC1作为一种跨膜糖蛋白在正常组织中的定位不完全相同。3、临床病理资料的统计学分析和独立预后不良因素判定：MUC1蛋白在食管鳞癌组织中的阳性表达率为72.4%(55/76),在正常食管组织中的阳性表达率为10.5%(2/19),两者差异有统计学意义(P0.01)；在T1、T2、T3+T4组中MUC1阳性表达率分别为42.9%(6/14)、71.4%(15/21)和82.9%(34/41),差异明显(P0.05)。肿瘤中高分化组与低分化组MUC1的阳性表达率分别为60.0%(21/35)和82.9%(34/41),两者差异有统计学意义(P0.05)；有、无淋巴结转移者的MUC1阳性表达率分别为86.1%(31/36)和60.0%(24/40),两者差异明显(P0.01),而MUC1的表达与患者的性别、年龄、病变长度及TNM分期无明显相关(P0.05)。患者总体5年生存率为25.0%(19/76),伴有MUC1表达阳性患者的5年生存率为16.4%(9/55),表达阴性患者5年生存率为47.6%(10/21),差异有统计学意义(P0.05)。COX回归分析显示,淋巴结转移(P=0.007)、T分期(P=0.043)及MUC1的阳性表达(P=0.01)是独立的预后不良因素。[结论]MUC1在食管鳞癌组织中的表达明显高于其在正常食管组织中的表达；MUC1在食管鳞癌组织中的表达以细胞核表达为主,随着T分期的升高,MUC1的阳性表达率也逐渐升高；肿瘤中-高分化组中MUC1的阳性表达率明显低于低分化组；MUC1在淋巴结转移阴性组中的阳性表达率明显低于阳性组,这提示肿瘤的侵袭性随着MUC1的表达升高而不断增强。伴有MUC1表达阳性患者的5年生存率明显低于表达阴性患者,MUC1可以作为评估患者预后的分子生物学标志。
[Abstract]:[Objective] background and pathological types of esophageal carcinoma and squamous cell carcinoma accounted for more than 90% patients with poor prognosis. The TNM classification is the main method to determine the prognosis of patients with esophageal squamous cell carcinoma, but still lack of sensitivity. So looking for accurate markers of tumor molecular biology prognosis in patients with esophageal squamous cell carcinoma has important significance for guiding the clinical treatment of a number of studies have found. Mucin 1 (MUC1) high expression in tumor cells, and tumor occurrence, development, invasion, metastasis, prognosis and other closely related. This study through the detection of MUC1 in esophageal squamous cell carcinoma and normal esophageal tissues, relation analysis method.] the expression level and clinical pathology and prognosis of January 2007 to January 2010 underwent surgical treatment and clinical pathological data of 76 cases of esophageal squamous cell carcinoma were studied retrospectively. Using Western blot (Western-blotting) And immunohistochemical staining (IHC) expression of MUC1 was detected in 76 cases of esophageal squamous cell carcinoma and 19 cases of normal esophageal mucosa, and according to the method of literature on decision making. The establishment of database analysis, using SPSS19.0 statistical software. X2 test was used to determine the correlation, survival analysis was performed by Kaplan-Meier method, using Log-rank test to judge the difference in survival, Cox proportional hazards model was used in multivariate analysis to determine the independent prognostic factors. Results:]1, Western-blotting detection of MUCl in esophageal squamous cell carcinoma tissues and normal esophageal tissues relative expression levels were 0.77 + 0.11 and 0.24 + 0.89, significant difference was statistically significant (F=7.6, P0.05).2, immunohistochemistry detection: the expression of MUC1 in esophageal squamous cell carcinoma than in normal esophageal tissues was significantly increased.MUC1 in normal esophageal tissues only in the cell membrane and nuclear weak While the expression of MUC1 in esophageal squamous cell carcinoma with nuclear expression, some expression in the cell membrane, and the positioning of MUC1 as a transmembrane glycoprotein in normal tissues is not the same as.3, determine the statistical analysis of clinical data and independent adverse prognostic factors: the positive expression of MUC1 protein in esophageal squamous cell carcinoma rate 72.4% (55/76), the positive expression in normal esophageal tissues was 10.5% (2/19), the difference was statistically significant (P0.01); in T1, T2, T3+T4 in the group of MUC1 positive expression rate was 42.9% (6/14), 71.4% (15/21) and 82.9% (34/41), significant difference (P0.05) the positive expression of tumor in highly and poorly differentiated groups of MUC1 rates were 60% (21/35) and 82.9% (34/41), the difference was statistically significant (P0.05); the positive expression of MUC1 had no lymph node metastasis rate are 86.1% (31/36) and 60% (24/40), two Cha Yiming Display (P0.01), and the expression of MUC1 and the patients' sex, age, lesion length and TNM stage (P0.05). There was no obvious correlation with the overall 5 year survival rate was 25% (19/76), accompanied by the expression of MUC1 positive patients 5 year survival rate was 16.4% (9/55), the expression of negative patients 5 year survival rate 47.6% (10/21), the difference was statistically significant (P0.05).COX regression analysis showed that lymph node metastasis (P=0.007), T stage (P=0.043) and the positive expression of MUC1 (P=0.01) expression is independent prognostic factor. Conclusion]MUC1 in esophageal squamous cell carcinoma is significantly higher than in normal esophageal tissues; the expression of MUC1 in esophageal squamous cell carcinoma with nuclear expression, with the T staging, the positive expression rate of MUC1 also increased gradually; the positive expression of tumor in highly differentiated group of MUC1 was significantly lower than the low differentiation group; positive negative expression group of MUC1 in lymph node metastasis The rate is significantly lower than that of the positive group. This indicates that the aggressiveness of tumors increases with the increase of MUC1 expression. The 5 year survival rate of patients with MUC1 expression is significantly lower than that of patients with negative expression. MUC1 can be used as a molecular biomarker for evaluating prognosis of patients.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.1

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