發(fā)布時(shí)間：2018-01-04 18:25

  本文關(guān)鍵詞：miR-106a在甲狀腺乳頭狀癌中表達(dá)及臨床意義　出處：《江蘇大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 甲狀腺乳頭狀癌 組織及血漿 MicroRNA-106a 生物標(biāo)記物

【摘要】：甲狀腺癌種類繁復(fù),主要包括甲狀腺乳頭狀癌(papillary thyroid carcinoma,PTC)、濾泡性癌、髓樣癌以及未分化癌四種類型。PTC是最常見、最典型的甲狀腺癌類型,約占所有甲狀腺癌的85%[1]。盡管預(yù)后良好,總體致死率較低,但其高發(fā)病率、高復(fù)發(fā)率、高遠(yuǎn)處轉(zhuǎn)移率以及高惡性程度的轉(zhuǎn)移灶致使PTC治療仍是困擾當(dāng)今醫(yī)學(xué)界的一大難題[1,2]。本課題組長期致力于PTC疾病防治的研究,積累了豐富的經(jīng)驗(yàn)。前期細(xì)胞水平研究證實(shí),PTC主要起源于濾泡上皮細(xì)胞,尤其是甲狀腺濾泡細(xì)胞。目前,PTC疾病診斷的主要手段是結(jié)合臨床資料對甲狀腺組織進(jìn)行組織病理形態(tài)學(xué)活檢。然而,近年來細(xì)針抽吸活檢術(shù)不斷暴露出其局限性,針吸不當(dāng)以及腫瘤組織質(zhì)地變硬引起的穿刺細(xì)胞脫落都有可能引起漏診,對PTC細(xì)胞辨認(rèn)能力差也會直接影響診斷結(jié)果。據(jù)不完全統(tǒng)計(jì),高達(dá)30%的術(shù)前活檢結(jié)果仍然無法確診[3,4]。由此可見,尋找核心分子生物學(xué)標(biāo)志物用以PTC疾病的確診將具有重大的臨床意義,這一策略也將有助于實(shí)施個(gè)性化治療并且避免不必要的手術(shù)。近年來,大量有關(guān)微小RNAs(MicroRNAs,miRNAs)在人類多種癌組織特別是PTC中表達(dá)異常的報(bào)道相繼被發(fā)現(xiàn)。早期的研究主要集中在病理組織學(xué)、基因水平、蛋白水平等方面,挖掘相對于正常組織而言,在PTC中miRNAs異常表達(dá)的類型。目前,這項(xiàng)工作已經(jīng)取得了一定的研究成果,例如,相對于正常組織,miRNA-21、miRNA-146b、miRNA-221、miRNA-222和miRNA-31在PTC中表達(dá)豐度均較高[5,6,7];相對于非侵襲性PTC,miRNA-138和miRNA-98在侵襲性PTC中表達(dá)豐度較低[8]。然而,限于實(shí)驗(yàn)技術(shù)和取材等因素,某些研究的結(jié)論甚至相互矛盾。顯然,前期工作所得到的研究結(jié)果還遠(yuǎn)遠(yuǎn)無法滿足PTC臨床預(yù)測與防治的迫切要求。由此可見,借助于合適的研究手段、確切的實(shí)驗(yàn)取材等優(yōu)勢,我們將從全新的角度系統(tǒng)深入的挖掘PTC中特定的miRNAs,為未來靶標(biāo)治療提供實(shí)驗(yàn)基礎(chǔ)與理論依據(jù)。miRNA-106a是一種致癌的miRNA。表達(dá)豐度鑒定發(fā)現(xiàn),其主要在食管癌[9]、胃癌[10]、大腸癌[11,12]和肺癌[13]等多種癌組織中高表達(dá)。功能機(jī)制研究發(fā)現(xiàn),高度表達(dá)的miRNA-106a通過促進(jìn)腫瘤細(xì)胞增殖、抑制腫瘤細(xì)胞凋亡以及誘導(dǎo)腫瘤血管生成等多種途徑推動腫瘤發(fā)生發(fā)展。綜上這些研究強(qiáng)烈暗示了miRNA-106a在癌癥發(fā)展中的重要地位。然而,目前為止,尚未有關(guān)于其在ptc發(fā)生發(fā)展中的研究。本研究的結(jié)果為miRNA-106a基因治療ptc提供實(shí)驗(yàn)依據(jù),為未來miRNA-106a作用機(jī)理研究提供全新的思路和明確的方向。目的:全面揭示miRNA-106a在ptc中的重要性,為將其作為疾病診斷和預(yù)后指標(biāo)提供實(shí)驗(yàn)依據(jù),為靶向基因治療提供有力支撐。方法:本研究檢測miRNA-106a在ptc患者腫瘤組織、癌旁正常組織及甲狀腺腺瘤組織中的表達(dá),同時(shí)檢測miRNA-106a在ptc患者、甲狀腺腺瘤患者及健康志愿者血漿中的含量,多層面多角度地探討miRNA-106a在ptc的診斷及預(yù)后評估中的應(yīng)用價(jià)值。(1)明確miRNA-106a表達(dá)的組織特異性收集30例在上海第八人民醫(yī)院就診的ptc患者的腫瘤組織、癌旁正常組織及30例甲狀腺腺瘤組織標(biāo)本,采用實(shí)時(shí)熒光定量聚合酶鏈?zhǔn)椒磻?yīng)(quantitativereal-timepolymerasechainreaction,qrt-pcr)檢測組織中miRNA-106a的豐度。明確miRNA-106a表達(dá)的組織分布特異性及其與ptc臨床病理特征的關(guān)系。(2)明確miRNA-106a表達(dá)的血漿學(xué)特征收集28例同期在上海第八人民醫(yī)院就診的ptc患者血漿、28例甲狀腺腺瘤患者血漿及28例健康者的血漿,采用qrt-pcr檢測血漿中miRNA-106a的豐度。分析組織和血漿中miRNA-106a表達(dá)水平的聯(lián)系與區(qū)別。明確血漿中miRNA-106a表達(dá)水平的特異性及其與ptc患者臨床病理特征的關(guān)系。結(jié)果:(1)miRNA-106a在ptc組織、癌旁正常組織及甲狀腺腺瘤組織中的相對表達(dá)量分別為3.63±0.36、1.04±0.08以及1.71±0.48。因此,ptc組織中miRNA-106a的表達(dá)水平明顯高于癌旁正常組織及甲狀腺腺瘤組織(p(27)0.01)。(2)miRNA-106a在ptc患者血漿、甲狀腺腺瘤患者血漿及健康志愿者血漿中的相對表達(dá)量分別為4.4±0.135的相對表達(dá)、2.5±0.058以及1.00±0.062,PTC患者血漿中miRNA-106a的表達(dá)水平顯著高于甲狀腺腺瘤患者血漿(P(27)0.001)。PTC組血漿中miRNA-106a表達(dá)均明顯高于健康體檢者(P0.001)。結(jié)論:(1)miRNA-106a在PTC組織及血漿中含量異常升高,可能與PTC的發(fā)生發(fā)展密切相關(guān)。(2)血漿miRNA-106a可成為PTC診斷及預(yù)后的血漿生物學(xué)新指標(biāo)。
[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.

【學(xué)位授予單位】：江蘇大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R736.1

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