miR-455-3p、miR-551-3p、miR-532-5p在甲状腺乳头状癌组织中的表达变化及临床相关性

发布时间：2018-04-03 01:29

本文选题：miRNAs　切入点：甲状腺乳头状癌　出处：《西南医科大学》2017年硕士论文

【摘要】：目的:微小RNA(micro RNA,mi RNAs)是一类内源性、单链、进化保守、非编码RNA,通过转录后水平负向调节基因表达,从而调控细胞增殖、分化和凋亡等。由于其集中参与了这些过程,所以mi RNAs在人类肿瘤进程中起到了重要作用,与肿瘤的发生、发展、诊断及预后判断等方面均存在密切的联系。相关文献及实验数据提示,mi RNAs在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)中具有一定的表达变化,在甲状腺乳头状癌的诊断和治疗中具有一定的价值和指导意义,但其作用机制尚不明确,与临床病理特征的关系有待进一步研究和分析。本研究旨在验证mi RNAs在甲状腺乳头状癌组织中的表达变化,筛选具有表达差异的mi RNAs并分析其临床相关性,用以区分甲状腺乳头状癌及良性肿瘤,开发、改进或加强甲状腺乳头状癌的诊断和治疗策略。方法:收集2015年6月至2016年12月在西南医科大学附属医院血管甲状腺外科行甲状腺手术的65例患者的甲状腺乳头状癌组织、良性肿瘤组织、肿瘤旁远端非瘤正常甲状腺组织(取距肿瘤最远端非瘤正常甲状腺组织),其中甲状腺乳头状癌30例,男性11例,女性19例;年龄13-71岁,平均年龄46.08±15.68岁;肿瘤直径2cm的15例,肿瘤直径≤2cm的15例(肿瘤直径以病理报告为准);多灶癌13例,单发癌17例;有淋巴结转移的19例,无淋巴结转移的11例;ATA甲状腺乳头状癌复发风险分级低危组18例,中高危组12例;TNM分期I期患者19例,II-IV期患者11例;传统型甲状腺乳头状癌患者25例,滤泡性乳头状癌患者5例;甲状腺球蛋白Tg≤77ng/ml的15例,Tg77ng/ml的15例;甲状腺微小乳头状癌5例。甲状腺良性肿瘤35例,结节性甲状腺肿24例,甲状腺腺瘤11例,男性5例,女性30例,年龄13-71岁,平均年龄46.03±13.40岁。所取标本均为术中非电刀灼烧新鲜离体组织,获取后立即存于液氮罐中速冻,并迅速转入-80℃冰箱内保存待用。所有患者的手术切除标本均行常规的组织病理学检查确定诊断。我们通过查阅TCGA数据,结合相关文献报道选取在甲状腺乳头状癌中有表达但尚未行进一步验证的mi RNAs共计8个,分别为mi R-532、mi R-455、mi R-551、mi R-1287、mi R-1975、mi R-1976、mi R-2355、mi R-1266,采用RT-q PCR检测其在甲状腺乳头状癌组织、良性肿瘤组织、肿瘤旁远端非瘤正常甲状腺组织中的表达,筛选出表达差异具有统计学意义的mi RNAs,分析与甲状腺乳头状癌临床病例特征的相关性。结果:研究发现,mi R-1287、mi R-1975、mi R-1976、mi R-2355、mi R-1266在甲状腺乳头状癌组织的表达虽然有一定变化,但尚无明显的统计学意义。与正常组织相比,mi R-532在甲状腺乳头状癌及良性肿瘤组织中表达明显降低,但良恶性肿瘤间的表达差异无明显统计学意义;与正常组织相比,mi R-455在甲状腺乳头状癌及良性肿瘤组织中表达明显升高,但良恶性肿瘤间的表达差异无明显统计学意义;与正常组织及良性肿瘤组织相比,mi R-551在甲状腺乳头状癌组织中表达均明显升高。临床病理特征相关性分析发现,mi R-455-3p的表达与TNM分期、肿瘤大小、年龄相关。mi R-532-5p的表达与年龄、淋巴结转移及TNM分期有关。ROC分析发现,mi R-455-3p、mi R-551-3p、mi R-532-5p对甲状腺肿瘤具有一定的诊断价值,其中mi R-455-3p最适合用于区分肿瘤组织与正常组织,其敏感性为75.0%,特异性为86.4%。结论:甲状腺乳头状癌中,mi R-455-3p、mi R-551-3p、mi R-532-5p表达水平存在明显变化,且与年龄、淋巴结转移及TNM分期等临床病理特征相关,有可能在甲状腺乳头状癌的诊断、术前评估及治疗策略的改进中起到一定作用。
[Abstract]:Objective: RNA (micro RNA, MI micro RNAs) is a kind of endogenous, single stranded, evolutionarily conserved, non RNA encoding, through post transcriptional expression negatively regulated genes, which regulate cell proliferation, differentiation and apoptosis. Due to its concentration involved in these processes, so mi RNAs in human tumors in the process of play an important role in tumor genesis and development, diagnosis and prognosis are closely related. The related literature and experimental data suggest that MI RNAs in papillary thyroid carcinoma (papillary thyroid, carcinoma, PTC) is a form of change, has certain value and significance in the diagnosis and treatment of thyroid papillary carcinoma, but its mechanism is not clear, and the relationship between clinical and pathological features of further research and analysis. The purpose of this study is to verify the MI expression of RNAs in papillary thyroid carcinoma, with screening table The differences of MI RNAs and analyze its clinical relevance, to distinguish between papillary thyroid carcinoma and benign tumors, development, improvement or strengthening strategies for diagnosis and treatment of papillary thyroid carcinoma. Methods: from June 2015 to December 2016 in papillary thyroid carcinoma and 65 cases of Affiliated Hospital of Medical College of Southwest vascular thyroid surgery of thyroid surgery the patients, benign tumors, tumor adjacent non tumor of distal normal thyroid tissues (taken from the tumor of distal non tumor normal thyroid tissue), including 30 cases of thyroid papillary carcinoma, 11 cases were male, 19 female; age 13-71 years, mean age 46.08 + 15.68 years; 15 cases of tumor diameter 2cm, 15 tumor diameter less than 2cm (the diameter of tumor pathology report to date); 13 cases of multifocal carcinoma, 17 cases of single cancer; 19 cases of lymph node metastasis, 11 cases without lymph node metastasis; ATA papillary thyroid cancer recurrence risk of low grade Risk group 18 cases, in 12 cases of high-risk group; TNM stage I patients with 19 cases, 11 cases of II-IV patients; the traditional type of patients with papillary thyroid carcinoma in 25 cases, 5 cases of follicular papillary carcinoma patients; 15 cases of thyroid globulin Tg less than or equal to 77ng/ml and Tg77ng/ml in 15 cases; 5 cases of papillary thyroid microcarcinoma thyroid carcinoma. 35 cases of thyroid benign tumor, 24 cases of nodular goiter, 11 cases of thyroid adenoma, 5 cases of male, 30 female, age 13-71 years, mean age 46.03 + 13.40 years old. The specimens were performed in non electric knife burn fresh tissue, stored in liquid nitrogen immediately get frozen after, and quickly transferred to -80 deg.c inside the refrigerator and save for all patients. Surgical resection specimens underwent conventional histopathology confirmed the diagnosis. We refer to the TCGA data, combining with relevant literature selection in papillary thyroid carcinoma with expression but not for further validation of the MI RNAs for a total of 8 points. Don't mi R-532, MI R-455, MI R-551, MI R-1287, MI R-1975, MI R-1976, MI R-2355, MI R-1266, using RT-q PCR detected in the papillary thyroid carcinoma, benign tumor tissues, tumor adjacent non tumor of the distal expression in normal thyroid tissue, were statistically significant differences in expression of MI RNAs the correlation analysis, and clinical features of thyroid papillary carcinoma. Results: Mi, R-1287, MI R-1975, MI R-1976, MI R-2355, MI R-1266 expression in papillary thyroid carcinoma have some changes, but there is no obvious statistical significance. Compared with normal tissues, the expression of MI R-532 in papillary thyroid cancer and benign tumor tissues decreased significantly, but the expression differences between benign and malignant tumors was not statistically significant; compared with normal tissues, the expression of MI R-455 in papillary thyroid carcinoma and benign tumor tissues was significantly increased, but There was no significant difference between the expression between benign and malignant tumors; compared with normal tissues and benign tumor tissues. The expression of MI R-551 in thyroid papillary carcinoma were significantly increased. The clinical and pathological characteristics of correlation between expression of TNM and MI, R-455-3p staging, tumor size, expression and age related.Mi R-532-5p, lymph node node metastasis and TNM stage.ROC analysis found that MI R-455-3p, MI R-551-3p, MI R-532-5p has a certain value in diagnosis of thyroid tumors, in which MI R-455-3p is most suitable for differentiating tumor tissue and normal tissue, the sensitivity was 75%, specificity was 86.4%. conclusion: thyroid papillary carcinoma, MI R-455-3p, MI R-551-3p, level there are obvious changes in the expression of MI and R-532-5p, related with age, lymph node metastasis and TNM stage clinical pathological features, possible diagnosis in thyroid papillary carcinoma, preoperative evaluation The evaluation and improvement of the treatment strategy play a role.

【学位授予单位】：西南医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R736.1

【相似文献】