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目的:研究人结直肠癌、腺瘤和癌旁正常组织中微小核糖核酸(microRNAs,miRNAs)的差异表达谱,并初步探讨其临床意义.方法:选取2008-01/07苏州大学附属第一医院和泰州市人民医院结直肠癌、对应癌旁正常组织以及结直肠腺瘤标本,提取组织总RNA,采用illumina microRNA芯片技术检测3种不同类型组织中miRNAs的表达,采用实时定量PCR技术对芯片检测结果进行验证.将结直肠癌组织中异常表达的miRNAs与结直肠癌患者的临床病理资料进行分析.结果:3种不同类型结直肠组织中miRNAs表达有明显差异,结直肠癌与癌旁正常组织相比,有65个miRNAs表达异常(P<0.001),其中35个上调,30个下调,而腺瘤与正常结直肠组织相比,有55个miRNAs表达差异(P<0.001),其中上调29个,下调26个.有25个miRNAs相对于正常组织同时在结直肠癌和腺瘤中异常表达,其中高表达12个,低表达有13个.与腺瘤相比,结直肠癌中有25个miRNAs表达异常(P<0.01),其中13个上调,12个下调.进一步定量PCR验证结果显示与正常结直肠黏膜组织相比,在癌组织中miR-552,miR-142-3p上调(2.97±2.72vs0.98±0.48;3.64±3.41vs1.31±0.61,均P<0.05),miR-139-3p和miR-133b下调(0.10±0.26vs0.82±0.70,0.81±0.67vs1.71±1.29,均P<0.05),与芯片结果相吻合.miR-552和miR-139-3p与结直肠癌患者年龄、性别、组织学、肿瘤大小和浸润深度无关(P>0.05),而miR-552与TNM分期、淋巴结和肝转移相关(P<0.05),miR-139-3p与TNM分期和肝转移相关(P<0.05),miR-142-3p除与组织学有关外,与其他临床病理参数无关,miR-133b与年龄相关,而与其他临床病理参数无关.结论:miRNAs参与了结直肠的癌变过程,特异的miRNAs的表达可能成为结直肠癌潜在的早期诊断和治疗新靶点.
Objective: To study the differential expression profiles of microRNAs (miRNAs) in human colorectal cancer, adenoma and adjacent normal tissues.Methods: The first affiliated hospital of Soochow University And Taizhou People’s Hospital of colorectal cancer, corresponding to adjacent normal tissue and colorectal adenoma specimens, tissue total RNA was extracted, the use of Illumina microRNA chip technology to detect miRNAs in three different types of tissues, using real-time quantitative PCR chip detection The results of validation.Extract miRNAs in colorectal cancer tissues and clinicopathological data of patients with colorectal cancer.Results: miRNAs expression in three different types of colorectal tissue were significantly different, colorectal cancer and adjacent normal tissue Compared with 65 miRNAs (P <0.001), of which 35 were up-regulated and 30 were down-regulated. However, compared with normal colorectal adenomas, there were 55 miRNAs expressed differently (P <0.001), of which 29 A, down 26. There are 25 miRNAs relative to normal tissue and abnormal expression in colorectal cancer and adenoma, including 12 high expression, low expression 13. Compared with adenoma, colorectal cancer in 25 MiRNAs (P <0.01), of which 13 were up-regulated and 12 were down-regulated.Further quantitative PCR results showed that compared with normal colorectal mucosa, miR-552 and miR-142-3p were up-regulated in cancer tissues (2.97 ± 2.72 miR-139-3p and miR-133b were down-regulated (0.10 ± 0.26vs0.82 ± 0.70,0.81 ± 0.67vs1.71 ± 1.29, vs0.98 ± 0.48; 3.64 ± 3.41vs1.31 ± 0.61, all P < (P <0.05), which was consistent with the results of the chip.miR-552 and miR-139-3p had no correlation with the age, sex, histology, tumor size and depth of invasion in patients with colorectal cancer (P> 0.05) TNM stage, lymph node metastasis and liver metastasis (P <0.05), miR-139-3p was associated with TNM stage and liver metastasis (P <0.05), and miR-142-3p was not related to other clinicopathological parameters , miR-133b is age-related but not related to other clinicopathological parameters.Conclusion: miRNAs are involved in the carcinogenesis of colorectal cancer, and the expression of specific miRNAs may be a new potential target for early diagnosis and treatment of colorectal cancer.