OLFM4在胆囊癌变多阶段中的表达及其临床意义
发布时间：2019-05-03 18:31
【摘要】：[目的]胆囊癌是一类具有高度恶性、高致死性、高侵袭性等特点的消化道恶性肿瘤,因发病隐匿、无特异临床表现导致其面临早诊困难,且无有效治疗方案。胆囊癌患者绝大多数被确诊时已是晚期,失去手术治愈的机会。而胆囊癌的发病机制尚不清楚,亟需探索相关病理机制和有效的诊疗策略。本课题旨在从胆囊癌与癌旁正常组织的差异表达基因中,寻找候选癌基因,并确定其在胆囊癌变多阶段中与临床病理参数联系的临床意义,初步探索该基因在胆囊癌发生发展中的作用,以期为胆囊癌患者的诊治提供新的研究线索。[方法]我们采用Agilent mRNA表达谱芯片技术对胆囊癌和配对的癌旁正常组织进行差异表达基因的mRNA表达谱分析;通过分子功能联合通路的表达关联分析筛选获得目的研究基因;进而采用免疫组织化学技术对比检测其在慢性胆囊炎、癌前病变和胆囊癌组织中的表达情况;利用SPSS19.0软件统计分析其与胆囊癌变多阶段、临床病理参数的相关性。[结果]1.通过Agilent mRNA表达谱芯片筛选提示OLFM4等379个基因在胆囊癌组织中高表达。利用Agilent mRNA表达谱芯片(SurePrint G3 Human Gene Expression 8x60K v2 Microarray)筛选技术,我们在5对胆囊癌及癌旁正常组织中,筛选出631个差异表达的mRNA。其中,上调表达基因379个,如OLFM4、CDH3、STYXL1 等;下调表达基因 252 个,如 YKT6、LUZP1、FBLN1 等;2. OLFM4基因在胆囊临床组织样本中蛋白细胞定位随癌变阶段发展从胞核转移至胞外,且随癌变阶段发展表达率和强度逐渐增高。2.1 OLFM4在胆囊癌变多阶段发展进程中细胞定位存在从胞核到胞外的转移现象。OLFM4在慢性胆囊炎组织中主要表达于细胞核,少量表达于细胞质,在癌前病变组织中,主要表达于细胞质和胞外,在胆囊癌组织中,主要分泌到细胞外;2.2 OLFM4表达率在癌变多阶段中表达逐步增加。OLFM4表达率在胆囊癌癌变多阶段(慢性胆囊炎,癌前病变,胆囊癌)组织中表达率逐步增加,且差异具有显著性(41.67% vs71.74%vs 80.56%,p0.001)。其中,OLFM4在癌前病变中表达高于慢性胆囊炎,差异具有显著性(p0. 001) ; OLFM4在胆囊癌中高表达于癌前病变,但差异未见显著性(p=0.192) ; OLFM4在胆囊癌中表达高于慢性胆囊炎,且差异具有显著性(p0. 001);2.3 OLFM4表达强度在胆囊癌变多阶段组织中逐步增强。 OLFM4表达强度在慢性胆囊炎、癌前病变和胆囊癌中依次增强,差异具有显著性(105.90vs 149.33 vs 166.01,p0.001)。其中,OLFM4在胆囊癌组织中的表达强度强于慢性胆囊炎组织,差异具有显著性(p0.001) ; OLFM4在胆囊癌前病变组织中的表达强度强于慢性胆囊炎组织,差异具有显著性(p0.001); OLFM4在胆囊癌中的表达强度强于癌前病变组织,但差异未见显著性(p=0.123);2.4 OLFM4表达水平与其他临床病理参数未见显著相关性。在胆囊癌临床组织样本中,OLFM4表达水平与患者年龄、性别、T分期、N分期、临床分期、分化程度均未见显著相关性(p 0.05)。[结论]1. OLFM4在胆囊癌变多阶段发展进程中可能发挥不同的作用,具有阶段特异性;2. OLFM4可能促进慢性胆囊炎-癌前病变-胆囊癌发展进程。
[Abstract]:[Objective] Gallbladder cancer is a kind of digestive tract malignant tumor with high degree of malignancy, high lethal and high invasiveness. The majority of the patients with gallbladder cancer have been diagnosed with an advanced stage and have no chance of surgical treatment. The pathogenesis of gallbladder carcinoma is not clear, and it is urgent to explore the relevant pathological mechanism and effective diagnosis and treatment strategy. The purpose of this study is to find the candidate oncogenes from the differential expression genes of the normal tissues of the gallbladder carcinoma and the adjacent tissues, and to determine the clinical significance of their association with the clinical and pathological parameters in the multi-stage gallbladder carcinoma, and to explore the role of the gene in the development of the gallbladder carcinoma. In order to provide a new clue for the diagnosis and treatment of the gallbladder carcinoma. [Methods] The expression profile of the differentially expressed genes in the normal tissues of the gallbladder and the adjacent non-adjacent normal tissues was analyzed by using the Agilent mRNA expression profile chip technique, and the target study gene was screened by the expression association analysis of the molecular function combined pathway. Furthermore, the expression of its expression in the tissues of chronic cholecystitis, pre-cancerous and gallbladder carcinoma was detected by immunohistochemical technique, and the correlation between the multi-stage and the clinicopathological parameters of the gallbladder carcinoma was statistically analyzed by using the SPSS19.0 software. [Results] 1. 379 genes, such as OLFM4, were expressed in the gallbladder carcinoma tissue by an Agilent mRNA expression profile. By using the Agilent mRNA expression spectrum chip (SurePrint G3 Human Gene Expression 8x60K v2 Microarray), we screened 631 differentially expressed mRNA in the normal tissues of the gallbladder carcinoma and the adjacent to the cancer. Of these,379 are up-regulated, such as OLFM4, CDH3, STYXL1, etc., and 252 down-regulated genes, such as YKT6, LUZP1, FBLN1, etc.; The localization of the OLFM4 gene in the sample of the gallbladder clinical tissue has been transferred from the nucleus to the extracellular domain with the development of the carcinogenesis stage, and the expression rate and the intensity are gradually increased with the development of the carcinogenesis stage. OLFM4 is mainly expressed in the nucleus of the chronic cholecystitis and is expressed in the cytoplasm, which is mainly expressed in the cytoplasm and the extracellular in the tissues of the precancerous lesion, and is mainly secreted outside the cell in the gallbladder carcinoma tissue, and the expression rate of the OLFM4 is gradually increased in the multi-stage of the cancer. The expression rate of OLFM4 was increased gradually in the multiple stage of gallbladder carcinoma (chronic cholecystitis, precancerous lesion and gallbladder carcinoma), and the difference was significant (41.67% vs.74% vs. 80.56%, p0.001). Among them, the expression of OLFM4 in the pre-cancerous lesions was higher than that of chronic cholecystitis and the difference was significant (p0. There was no significant difference in the expression of OLFM4 in the gallbladder carcinoma (p = 0.192), and the expression of OLFM4 in the gallbladder carcinoma was higher than that of the chronic cholecystitis, and the difference was significant (p0. 001); 2.3 OLFM4 expression intensity was gradually increased in the multi-stage tissue of gallbladder carcinoma. The expression intensity of OLFM4 was significantly increased in chronic cholecystitis, pre-cancerous and gallbladder carcinoma (105.90 vs. 149.33 vs. 166.01, p0.001). The expression of OLFM4 in the gallbladder carcinoma was stronger than that of the chronic cholecystitis (p0.001), and the expression of OLFM4 in the premalignant tissue of the gallbladder was stronger than that of the chronic cholecystitis (p0.001). The expression of OLFM4 in gallbladder carcinoma was stronger than that of precancerous lesion, but the difference was not significant (p = 0.123), and the expression level of 2.4 OLFM4 was not significantly correlated with other clinical pathological parameters. In the sample of gallbladder carcinoma, the expression level of OLFM4 was not significantly correlated with age, sex, T stage, N stage, clinical stage and degree of differentiation (p.05). [Conclusion] 1. OLFM4 may play a different role in the development of the multi-stage of gallbladder carcinoma, and has stage specificity;2. OLFM4 may promote the progression of chronic cholecystitis-premalignant lesions-the development of the gallbladder carcinoma.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.8
本文编号：2469156
[Abstract]:[Objective] Gallbladder cancer is a kind of digestive tract malignant tumor with high degree of malignancy, high lethal and high invasiveness. The majority of the patients with gallbladder cancer have been diagnosed with an advanced stage and have no chance of surgical treatment. The pathogenesis of gallbladder carcinoma is not clear, and it is urgent to explore the relevant pathological mechanism and effective diagnosis and treatment strategy. The purpose of this study is to find the candidate oncogenes from the differential expression genes of the normal tissues of the gallbladder carcinoma and the adjacent tissues, and to determine the clinical significance of their association with the clinical and pathological parameters in the multi-stage gallbladder carcinoma, and to explore the role of the gene in the development of the gallbladder carcinoma. In order to provide a new clue for the diagnosis and treatment of the gallbladder carcinoma. [Methods] The expression profile of the differentially expressed genes in the normal tissues of the gallbladder and the adjacent non-adjacent normal tissues was analyzed by using the Agilent mRNA expression profile chip technique, and the target study gene was screened by the expression association analysis of the molecular function combined pathway. Furthermore, the expression of its expression in the tissues of chronic cholecystitis, pre-cancerous and gallbladder carcinoma was detected by immunohistochemical technique, and the correlation between the multi-stage and the clinicopathological parameters of the gallbladder carcinoma was statistically analyzed by using the SPSS19.0 software. [Results] 1. 379 genes, such as OLFM4, were expressed in the gallbladder carcinoma tissue by an Agilent mRNA expression profile. By using the Agilent mRNA expression spectrum chip (SurePrint G3 Human Gene Expression 8x60K v2 Microarray), we screened 631 differentially expressed mRNA in the normal tissues of the gallbladder carcinoma and the adjacent to the cancer. Of these,379 are up-regulated, such as OLFM4, CDH3, STYXL1, etc., and 252 down-regulated genes, such as YKT6, LUZP1, FBLN1, etc.; The localization of the OLFM4 gene in the sample of the gallbladder clinical tissue has been transferred from the nucleus to the extracellular domain with the development of the carcinogenesis stage, and the expression rate and the intensity are gradually increased with the development of the carcinogenesis stage. OLFM4 is mainly expressed in the nucleus of the chronic cholecystitis and is expressed in the cytoplasm, which is mainly expressed in the cytoplasm and the extracellular in the tissues of the precancerous lesion, and is mainly secreted outside the cell in the gallbladder carcinoma tissue, and the expression rate of the OLFM4 is gradually increased in the multi-stage of the cancer. The expression rate of OLFM4 was increased gradually in the multiple stage of gallbladder carcinoma (chronic cholecystitis, precancerous lesion and gallbladder carcinoma), and the difference was significant (41.67% vs.74% vs. 80.56%, p0.001). Among them, the expression of OLFM4 in the pre-cancerous lesions was higher than that of chronic cholecystitis and the difference was significant (p0. There was no significant difference in the expression of OLFM4 in the gallbladder carcinoma (p = 0.192), and the expression of OLFM4 in the gallbladder carcinoma was higher than that of the chronic cholecystitis, and the difference was significant (p0. 001); 2.3 OLFM4 expression intensity was gradually increased in the multi-stage tissue of gallbladder carcinoma. The expression intensity of OLFM4 was significantly increased in chronic cholecystitis, pre-cancerous and gallbladder carcinoma (105.90 vs. 149.33 vs. 166.01, p0.001). The expression of OLFM4 in the gallbladder carcinoma was stronger than that of the chronic cholecystitis (p0.001), and the expression of OLFM4 in the premalignant tissue of the gallbladder was stronger than that of the chronic cholecystitis (p0.001). The expression of OLFM4 in gallbladder carcinoma was stronger than that of precancerous lesion, but the difference was not significant (p = 0.123), and the expression level of 2.4 OLFM4 was not significantly correlated with other clinical pathological parameters. In the sample of gallbladder carcinoma, the expression level of OLFM4 was not significantly correlated with age, sex, T stage, N stage, clinical stage and degree of differentiation (p.05). [Conclusion] 1. OLFM4 may play a different role in the development of the multi-stage of gallbladder carcinoma, and has stage specificity;2. OLFM4 may promote the progression of chronic cholecystitis-premalignant lesions-the development of the gallbladder carcinoma.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.8
【参考文献】
相关期刊论文 前1条
1 朱凯;张爱萍;林秀敏;;非小细胞肺癌患者血浆OLFM4水平及其临床意义分析[J];临床肿瘤学杂志;2016年06期
，本文编号：2469156
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