miR-106a在甲状腺乳头状癌中表达及临床意义

发布时间：2018-01-04 18:25

本文关键词：miR-106a在甲状腺乳头状癌中表达及临床意义　出处：《江苏大学》2017年硕士论文　论文类型：学位论文

【摘要】：甲状腺癌种类繁复,主要包括甲状腺乳头状癌(papillary thyroid carcinoma,PTC)、滤泡性癌、髓样癌以及未分化癌四种类型。PTC是最常见、最典型的甲状腺癌类型,约占所有甲状腺癌的85%[1]。尽管预后良好,总体致死率较低,但其高发病率、高复发率、高远处转移率以及高恶性程度的转移灶致使PTC治疗仍是困扰当今医学界的一大难题[1,2]。本课题组长期致力于PTC疾病防治的研究,积累了丰富的经验。前期细胞水平研究证实,PTC主要起源于滤泡上皮细胞,尤其是甲状腺滤泡细胞。目前,PTC疾病诊断的主要手段是结合临床资料对甲状腺组织进行组织病理形态学活检。然而,近年来细针抽吸活检术不断暴露出其局限性,针吸不当以及肿瘤组织质地变硬引起的穿刺细胞脱落都有可能引起漏诊,对PTC细胞辨认能力差也会直接影响诊断结果。据不完全统计,高达30%的术前活检结果仍然无法确诊[3,4]。由此可见,寻找核心分子生物学标志物用以PTC疾病的确诊将具有重大的临床意义,这一策略也将有助于实施个性化治疗并且避免不必要的手术。近年来,大量有关微小RNAs(MicroRNAs,miRNAs)在人类多种癌组织特别是PTC中表达异常的报道相继被发现。早期的研究主要集中在病理组织学、基因水平、蛋白水平等方面,挖掘相对于正常组织而言,在PTC中miRNAs异常表达的类型。目前,这项工作已经取得了一定的研究成果,例如,相对于正常组织,miRNA-21、miRNA-146b、miRNA-221、miRNA-222和miRNA-31在PTC中表达丰度均较高[5,6,7];相对于非侵袭性PTC,miRNA-138和miRNA-98在侵袭性PTC中表达丰度较低[8]。然而,限于实验技术和取材等因素,某些研究的结论甚至相互矛盾。显然,前期工作所得到的研究结果还远远无法满足PTC临床预测与防治的迫切要求。由此可见,借助于合适的研究手段、确切的实验取材等优势,我们将从全新的角度系统深入的挖掘PTC中特定的miRNAs,为未来靶标治疗提供实验基础与理论依据。miRNA-106a是一种致癌的miRNA。表达丰度鉴定发现,其主要在食管癌[9]、胃癌[10]、大肠癌[11,12]和肺癌[13]等多种癌组织中高表达。功能机制研究发现,高度表达的miRNA-106a通过促进肿瘤细胞增殖、抑制肿瘤细胞凋亡以及诱导肿瘤血管生成等多种途径推动肿瘤发生发展。综上这些研究强烈暗示了miRNA-106a在癌症发展中的重要地位。然而,目前为止,尚未有关于其在ptc发生发展中的研究。本研究的结果为miRNA-106a基因治疗ptc提供实验依据,为未来miRNA-106a作用机理研究提供全新的思路和明确的方向。目的:全面揭示miRNA-106a在ptc中的重要性,为将其作为疾病诊断和预后指标提供实验依据,为靶向基因治疗提供有力支撑。方法:本研究检测miRNA-106a在ptc患者肿瘤组织、癌旁正常组织及甲状腺腺瘤组织中的表达,同时检测miRNA-106a在ptc患者、甲状腺腺瘤患者及健康志愿者血浆中的含量,多层面多角度地探讨miRNA-106a在ptc的诊断及预后评估中的应用价值。(1)明确miRNA-106a表达的组织特异性收集30例在上海第八人民医院就诊的ptc患者的肿瘤组织、癌旁正常组织及30例甲状腺腺瘤组织标本,采用实时荧光定量聚合酶链式反应(quantitativereal-timepolymerasechainreaction,qrt-pcr)检测组织中miRNA-106a的丰度。明确miRNA-106a表达的组织分布特异性及其与ptc临床病理特征的关系。(2)明确miRNA-106a表达的血浆学特征收集28例同期在上海第八人民医院就诊的ptc患者血浆、28例甲状腺腺瘤患者血浆及28例健康者的血浆,采用qrt-pcr检测血浆中miRNA-106a的丰度。分析组织和血浆中miRNA-106a表达水平的联系与区别。明确血浆中miRNA-106a表达水平的特异性及其与ptc患者临床病理特征的关系。结果:(1)miRNA-106a在ptc组织、癌旁正常组织及甲状腺腺瘤组织中的相对表达量分别为3.63±0.36、1.04±0.08以及1.71±0.48。因此,ptc组织中miRNA-106a的表达水平明显高于癌旁正常组织及甲状腺腺瘤组织(p(27)0.01)。(2)miRNA-106a在ptc患者血浆、甲状腺腺瘤患者血浆及健康志愿者血浆中的相对表达量分别为4.4±0.135的相对表达、2.5±0.058以及1.00±0.062,PTC患者血浆中miRNA-106a的表达水平显著高于甲状腺腺瘤患者血浆(P(27)0.001)。PTC组血浆中miRNA-106a表达均明显高于健康体检者(P0.001)。结论:(1)miRNA-106a在PTC组织及血浆中含量异常升高,可能与PTC的发生发展密切相关。(2)血浆miRNA-106a可成为PTC诊断及预后的血浆生物学新指标。
[Abstract]:Many types of thyroid cancer, including papillary thyroid carcinoma (papillary thyroid, carcinoma, PTC), follicular carcinoma, medullary carcinoma, undifferentiated carcinoma in four types of.PTC is the most common, the most typical type of thyroid cancer, accounting for about 85%[1]. of all thyroid cancer despite the good prognosis, the overall mortality rate was low, but the the high incidence rate, high recurrence rate, the research group [1,2]. a big problem at high transfer rate and high metastatic malignancy resulting in PTC treatment is still plagued the medical profession's long-term commitment to PTC prevention, has accumulated rich experience. The cellular level study confirmed that PTC mainly originated from follicular epithelial cells. Especially the thyroid follicular cells. At present, the main means of disease diagnosis is PTC with clinical data were pathological biopsy of the thyroid tissue. However, in recent years, fine needle aspiration biopsy with continuous exposure Its limitations, and improper puncture needle aspiration cell tumor tissue hard texture caused by shedding are likely to cause misdiagnosis of PTC cells to identify ability will directly affect the diagnosis results. According to incomplete statistics, up to 30% of the preoperative biopsy results is still not confirmed [3,4]. thus looking for biomarkers of core molecules for the PTC disease diagnosis has great clinical significance, this strategy will also contribute to the implementation of personalized treatment and avoid unnecessary surgery. In recent years, a large number of related small RNAs (MicroRNAs, miRNAs) in a variety of human cancer especially the abnormal expression of PTC reported in earlier studies have been found. Mainly in histopathology, gene level, protein level, mining relative to normal tissue, the types of abnormal expression of miRNAs in PTC. At present, this work has made some research The results, for example, compared with normal tissue, miRNA-21, miRNA-146b, miRNA-221, miRNA-222 and [5,6,7] were high expression of miRNA-31 in PTC; compared with non invasive PTC, low abundance of [8]. but the expression of miRNA-138 and miRNA-98 in the invasion of PTC, due to the limitation of the experimental technology and materials and other factors, some conclusions are even contradictory. Obviously, the results obtained in previous work is far unable to meet the urgent requirement of PTC clinical prediction and prevention. Thus, with the help of appropriate methods, the exact experimental materials and other advantages, we will explore miRNAs specific PTC from a new perspective, for the future therapeutic target provides the experimental basis and theoretical basis.MiRNA-106a is a kind of carcinogenic miRNA. expression abundance identified mainly in esophageal carcinoma [9], gastric carcinoma [10], colon cancer and lung cancer [11,12] [13] and other cancer tissues of high Study on the function mechanism of expression. Found that highly expressed miRNA-106a by promoting the proliferation of tumor cells, inhibit the apoptosis of tumor cells and induce tumor angiogenesis and promote tumor development. All these studies strongly suggest that miRNA-106a in cancer development in the important position. However, so far, there has not been a research on its development in the the occurrence of PTC. The results of this study provide experimental basis for gene therapy of miRNA-106a PTC, to provide new ideas and clear direction for the future research of miRNA-106a mechanism. Objective: to fully reveal the importance of miRNA-106a in PTC, which will provide experimental basis as indicators of disease diagnosis and prognosis, and provide strong support for targeted gene therapy. Methods: the detection of miRNA-106a in tumor tissue of PTC patients, the expression of normal tissues and thyroid adenoma tissues, and detection of miR NA-106a in patients with PTC, the content of thyroid adenoma patients and healthy volunteers in plasma, multi-level multi angle to explore the application value of miRNA-106a in diagnosis and prognosis of PTC. (1) miRNA-106a clear tissue specific expression of 30 cases were collected in the hospital of Shanghai Eighth People's Hospital of the PTC patient's tumor and adjacent normal tissue and 30 cases of thyroid adenoma tissues by real-time fluorescence quantitative polymerase chain reaction (quantitativereal-timepolymerasechainreaction, qRT-PCR) detection of miRNA-106a in abundance. Clear expression of miRNA-106a tissue specific distribution and its relationship with the clinical pathological features of PTC. (2) the expression of miRNA-106a in plasma clear features of 28 cases were collected in the same period were the eighth people in Shanghai hospital patients with PTC, 28 cases of thyroid adenoma patients and 28 cases of normal plasma detected by qRT-PCR plasma The abundance of miRNA-106a. Analysis of tissue and plasma miRNA-106a expression level. The relation and difference between clear plasma miRNA-106a specific expression level and its relationship with clinicopathological features in patients with PTC. Results: (1) miRNA-106a in the PTC group, the relative expression of adjacent normal tissues and thyroid adenoma tissues were respectively 3.63. 0.36,1.04 + 0.08 and 1.71 + 0.48., therefore, the expression level of miRNA-106a in PTC tissues was significantly higher than that of adjacent normal tissues and thyroid adenoma tissues (P (27) 0.01). (2) miRNA-106a in plasma of patients with PTC, the relative expression in plasma of patients with thyroid adenoma and healthy volunteers in plasma were 4.4 + 0.135 relative expression 2.5, + 0.058 and 1 + 0.062, the expression level of miRNA-106a in plasma of patients with PTC was significantly higher than that in plasma of patients with thyroid adenoma (P (27) 0.001).PTC group in plasma miRNA-106a expression was Gao Yujian Physical examination (P0.001). Conclusion: (1) the abnormal increase of miRNA-106a in PTC tissue and plasma may be closely related to the occurrence and development of PTC. (2) plasma miRNA-106a can be a new index of plasma biology for diagnosis and prognosis of PTC.

【学位授予单位】：江苏大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R736.1

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