丙酮酸激酶M1和M2在结直肠癌中的表达及临床意义

发布时间：2018-03-09 12:34

本文选题：结直肠癌　切入点：丙酮酸激酶M1　出处：《四川医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的:通过免疫组化方式对结直肠癌(Colorectal Carcinoma,CRC)组织病理切片进行分析,研究丙酮酸激酶M1(Pyruvate kinase M1,M1-PK)和丙酮酸激酶M2(Pyruvate kinase M2,M2-PK)在不同临床及病理分期的CRC组织及癌旁正常结直肠组织中的表达与CRC临床病理特征的关系,探讨M1-PK和M2-PK在CRC中的表达与其疾病发展的关系。方法:本实验标本全部来自宜宾市第一人民医院病理科的手术切除组织,时间段集中在2013年1月-2015年1月,共选择CRC组织标本69份,同时选择癌旁正常结直肠组织标本69份作为对照样本,所有病理标本必须具备完整甲级临床病历。病历记录详细、规范,手术资料及影像学资料完备。患者年龄45-82岁之间,中位年龄65岁,包含32例男性及37例女性,治疗过程要求详细。CRC组织学类型包含41例管状腺癌、20例乳头状腺癌,还有其它病理类型癌8例;CRC分化程度包含48例中分化癌、21例低分化癌。采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连结法(streptavidin-peroxidase,SP)检测M1-PK和M2-PK在CRC组织中的表达,在低分化组、中分化组与正常癌旁组织间对比。采用单因素和多因素分析比较M1-PK和M2-PK在CRC的低分化组、中分化组与正常癌旁组织中表达与临床病理特征之间的关系。采用相关分析比较CRC中M1-PK与M2-PK表达的相关性。结果:1.M1-PK与M2-PK在CRC组织及癌旁正常组织中的表达与分布:M1-PK与M2-PK在正常结肠上皮细胞及CRC上皮细胞中均可见表达,呈细胞质分布,棕黄色颗粒为阳性信号表现。M1-PK在结直肠癌组织中表达微弱,低于癌旁正常组织(平均光密度值(Average optical density,AOD):对照组0.320±0.026;癌组织组0.231±0.023 P0.05);M2-PK在结直肠癌组织中表达明显高于癌旁正常组织(AOD:对照组0.207±0.056;癌组织组0.347±0.054 P0.05);M1-PK在CRC组织中表达随着肿瘤分化程度降低而减少(AOD:对照组0.320±0.026;中等分化组0.260±0.016;低分化组0.167±0.059;P0.05);M2-PK在CRC组织中表达随着肿瘤分化程度降低而增加(AOD:对照组0.207±0.056;中等分化组0.259±0.068;低分化组0.420±0.019;P0.05);2.采用单因素和多因素分析比较M1-PK和M2-PK在CRC的低分化组、中分化组与正常癌旁组织中表达与临床病理特征之间的关系显示:M1-PK在CRC组织中的阳性表达与分化程度密切相关(P0.05),而与患者年龄、肿瘤大小、肿瘤部位、TNM临床分期及淋巴结转移无关。M2-PK在CRC组织中的阳性表达与肿瘤大小、肿瘤临床TNM分期及肿瘤分化程度密切相关(P0.05),而与患者年龄、肿瘤部位、是否存在淋巴结转移无明显关系。3.CRC组织中M1-PK的表达水平与M2-PK表达的相关性:采用直线相关分析结果显示:M1-PK与M2-PK表达AOD比较,r=-0.689,P0.01,提示呈负相关关系。结论:1.M1-PK与M2-PK在CRC上皮细胞以及正常结肠上皮细胞中均有所表达,而并非只特异表达其中之一。2.M2-PK在CRC细胞中表达量能初步反应肿瘤大小、肿瘤分期及肿瘤分化程度。3.从组织表达的角度提示,M2-PK与人CRC的恶性程度及进展呈正相关,而M1-PK与人CRC的恶性程度及进展呈负相关。
[Abstract]:Objective: by immunohistochemical methods on colorectal cancer (Colorectal Carcinoma, CRC) histopathological analysis of pyruvate kinase M1 (Pyruvate kinase M1 M1-PK M2 (Pyruvate) and pyruvate kinase kinase M2, M2-PK) in different clinical and pathologic staging of CRC tissues and adjacent normal colorectal tissues and the expression of the clinical pathological features of CRC, to explore the relationship between M1-PK and M2-PK expression in CRC and the development of the disease. Methods: in this experiment, all specimens from the pathology department of Yibin First People's Hospital of the resected tissue, concentrated period of time in January 2013 -2015 year in January, total 69 CRC samples, and adjacent normal colorectal tissue specimens from 69 as the control samples, all specimens must have complete clinical records. A detailed specification, operation data and imaging data of 45-82 patients with complete age. Years old, the median age was 65 years, including 32 cases of male and 37 cases female, histological type contains 41 cases of tubular adenocarcinoma treatment process requires detailed.CRC tissue, 20 cases of papillary adenocarcinoma, and other pathological types of carcinoma in 8 cases; the differentiation of CRC containing 48 cases of undifferentiated carcinoma in 21 cases, poorly differentiated carcinoma. Using immunohistochemical streptavidin peroxidase conjugated method (streptavidin-peroxidase, SP) to detect the expression of M1-PK and M2-PK in CRC tissues, in low differentiation group, middle differentiation group and normal adjacent tissues. Compared with single factor and multi factor analysis and comparison of M1-PK and M2-PK in low differentiation group CRC the expression, relationship with clinicopathological features in differentiation group and normal paracancerous tissues. The correlation using correlation analysis expression of M1-PK compared with M2-PK CRC. Results: the expression of 1.M1-PK and M2-PK in CRC and normal tissues and the distribution of M1-PK and M2-PK In normal colonic epithelial cells and epithelial cells were found in the expression of CRC, a cytoplasmic distribution, brown yellow particles for positive signal expression of.M1-PK in colorectal cancer tissues was weak, lower than that in adjacent normal tissues (average optical density value (Average optical density, AOD): the control group 0.320 + 0.026; 0.231 + cancer group 0.023 P0.05); the expression of M2-PK in colorectal cancer tissues was significantly higher than that in normal tissues (AOD: control group 0.207 + 0.056; 0.347 + 0.054 P0.05 Cancer Group); the expression of M1-PK decreased with the degree of tumor differentiation decreased in the CRC group (AOD: control group 0.320 + 0.026; 0.260 + 0.016 moderately differentiated group; low differentiation group 0.167 + 0.059; P0.05); the expression of M2-PK in CRC tissues increased with the degree of tumor differentiation decreased (AOD: control group 0.207 + 0.056; 0.259 + 0.068 moderately differentiated group; low differentiation group was 0.420 + 0.019; P0.05; 2.) by single factor and multi factor score Analysis and comparison of M1-PK and M2-PK in low differentiation group CRC, display and the relationship between the clinical pathological features of expression differentiation group and normal paracancerous tissues, closely related to the degree of positive expression in CRC tissues and the differentiation of M1-PK (P0.05), and the patient's age, tumor size, tumor location, clinical stage and TNM lymph node expression and tumor size independent.M2-PK in CRC tissues was closely related to metastasis, clinical TNM staging and tumor differentiation (P0.05), and the patient's age, tumor location, whether there is correlation between the expression of M2-PK and lymph node metastasis had no obvious relationship with.3.CRC in the M1-PK group: Using linear correlation analysis the results showed that M1-PK and M2-PK expression of AOD, r=-0.689, P0.01, there was a negative correlation between the tips. Conclusion: both the 1.M1-PK and M2-PK CRC expression in epithelial cells and normal colonic epithelial cells, which is not only a specific One of them,.2.M2-PK expression in CRC cells, can initially reflect tumor size, tumor stage and tumor differentiation..3. indicates from the perspective of tissue expression that M2-PK is positively correlated with the malignancy and progression of human CRC, while M1-PK is negatively correlated with the malignancy and progression of human CRC.

【学位授予单位】：四川医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.34

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