本文關(guān)鍵詞： 食管鱗癌 TAZ Lats2 免疫組化　出處：《第二軍醫(yī)大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：食管癌為全球范圍內(nèi)發(fā)病率第八位的惡性腫瘤,并占因腫瘤死亡的第六位。中國(guó)是食管癌的高發(fā)國(guó)家,食管癌在我國(guó)是第四大惡性腫瘤,食管癌90%以上病理類型為鱗狀細(xì)胞癌。食管鱗癌的早期癥狀隱匿,進(jìn)展迅速,且治療手段較為局限,診治過程中存在較多難題,尤其在分子層面上,該疾病的預(yù)后標(biāo)志物目前仍在探索中。對(duì)相應(yīng)腫瘤分子標(biāo)志物的探索,在優(yōu)化食管鱗癌的個(gè)體化治療,以及對(duì)該類疾病患者的預(yù)后評(píng)估過程中,具有重要意義。具有PDZ模序的轉(zhuǎn)錄共激活因子(transcriptional coactivator with PDZ binding motif,TAZ)是一類癌基因,是Hippo通路的主要效應(yīng)因子,在調(diào)控組織器官大小形狀,調(diào)節(jié)細(xì)胞生長(zhǎng)及接觸性抑制的機(jī)制中發(fā)揮作用。研究發(fā)現(xiàn)TAZ在多類腫瘤組織內(nèi)的表達(dá)增高,并在腫瘤疾病的發(fā)生及發(fā)展過程中發(fā)揮作用。TAZ通過在細(xì)胞核內(nèi)與轉(zhuǎn)錄激活因子結(jié)合后,可激活基因轉(zhuǎn)錄,刺激細(xì)胞增殖及侵襲轉(zhuǎn)移,并介導(dǎo)腫瘤細(xì)胞的干細(xì)胞分化過程。大腫瘤抑制因子2(large tumorsuppressor kinase 2,Lats2)為拉特抑癌家族(Lats Family)成員之一,通過調(diào)控細(xì)胞周期檢查點(diǎn)(G1/S)阻滯細(xì)胞的有絲分裂。研究發(fā)現(xiàn),Lats2在多種腫瘤組織內(nèi)表達(dá)下調(diào),并在腫瘤的發(fā)生發(fā)展中起抑癌作用。與TAZ一樣,Lats2也為Hippo通路的組成元件,并為位于TAZ上游的負(fù)向控制基因,通過磷酸化后者使其失去轉(zhuǎn)錄共激活活性。此外,Lats2可參與影響其他通路(如EGFR信號(hào)通路、Wnt通路、P53通路等)發(fā)揮其抑癌功能。本次研究通過免疫組化(MaxVision法)觀察食管鱗癌組織內(nèi)TAZ和Lats2的表達(dá)情況及相互關(guān)系,并分析其對(duì)食管鱗癌患者臨床病理特征及預(yù)后的關(guān)系。TAZ的高表達(dá)與腫瘤的浸潤(rùn)深度、淋巴結(jié)轉(zhuǎn)移陽(yáng)性、分化程度較低、較大的腫瘤直徑及較晚的腫瘤分期具有相關(guān)性(p0.05),TAZ表達(dá)高者,食管鱗癌患者預(yù)后較差。Lats2的表達(dá)水平與患者淋巴結(jié)轉(zhuǎn)移、組織分化程度及腫瘤分期相關(guān),Lats2表達(dá)高者,預(yù)示著較少的淋巴結(jié)轉(zhuǎn)移可能、較高的分化程度和較早的分期(p0.05)。在生存期的研究中發(fā)現(xiàn),腫瘤組織內(nèi)Lats2表達(dá)高者較Lats2表達(dá)低者具有更長(zhǎng)的生存期。相關(guān)性分析結(jié)果提示TAZ與Lats2的表達(dá)存在負(fù)相關(guān)性(p0.001),即當(dāng)腫瘤組織內(nèi)TAZ為高表達(dá)時(shí),Lats2更傾向于低表達(dá)。多因素COX回歸模型結(jié)果顯示,TAZ高表達(dá)、Lats2低表達(dá)、淋巴結(jié)轉(zhuǎn)移陽(yáng)性及腫瘤直徑超過5cm均為食管鱗癌患者不良預(yù)后的獨(dú)立影響因子。根據(jù)上述研究結(jié)果,我們認(rèn)為在食管鱗癌中,TAZ是食管鱗癌患者預(yù)后不良的影響因子,而Lats2是食管鱗癌患者預(yù)后良好的影響因子,二者都可能在腫瘤的進(jìn)展及侵襲轉(zhuǎn)移中起到一定作用,并有望作為預(yù)后評(píng)估的標(biāo)志物。
[Abstract]:Esophageal cancer is one of the most common malignant tumors in the world, accounting for 6th of the total cancer deaths. China is a country with a high incidence of esophageal cancer, and esophageal cancer is one of the 4th largest malignant tumors in China. The pathological type of esophageal carcinoma above 90% is squamous cell carcinoma. The early symptoms of esophageal squamous cell carcinoma are hidden, the progress is rapid, and the treatment is limited. There are many problems in the diagnosis and treatment, especially at the molecular level. At present, the prognostic markers of this disease are still being explored. The exploration of the corresponding tumor molecular markers, the optimization of individual treatment of esophageal squamous cell carcinoma, and the evaluation of prognosis of the patients with this disease, Transcriptional coactivator with PDZ binding motif (TAZ), a transcriptional coactivator with PDZ binding motif, is a class of oncogenes and a major effector of the Hippo pathway, which regulates the size and shape of tissues and organs. Regulation of cell growth and mechanism of contact inhibition. Studies have found that the expression of TAZ is increased in many kinds of tumor tissues. TAZ can activate gene transcription, stimulate cell proliferation, invasion and metastasis by binding to transcriptional activators in the nucleus. Large tumorsuppressor kinase 2 Lats2 is a member of Lats Family2, a large tumor suppressor family, which mediates the stem cell differentiation of tumor cells. By regulating the cell cycle checkpoint G 1 / S, the mitosis of the cells was blocked. It was found that the expression of LATS2 was down-regulated in various tumor tissues and played an inhibitory role in tumorigenesis and progression. Like TAZ, it is also a component of the Hippo pathway. And for the negative control gene upstream of TAZ, In addition, Lats2 may be involved in influencing other pathways (such as EGFR signaling pathway, Wnt pathway, p53 pathway, etc.) to play a role in the inhibition of cancer. In this study, we observed feeding by immunohistochemistry with MaxVision method. Expression of TAZ and Lats2 in tubular squamous cell carcinoma and their relationship. The relationship between the high expression of TAZ and the depth of invasion, lymph node metastasis and differentiation of esophageal squamous cell carcinoma was analyzed. The larger tumor diameter and the later tumor stage were associated with high expression of TAZ. The prognosis of esophageal squamous cell carcinoma patients was poor. The expression level of Lats2 was associated with lymph node metastasis, tissue differentiation and tumor staging, and the expression of LatS2 was higher in patients with esophageal squamous cell carcinoma. It indicates that less lymph node metastasis is possible, higher differentiation degree and earlier stage (p0.05). In the study of survival time, we found, The results of correlation analysis showed that there was a negative correlation between the expression of TAZ and Lats2, that is, when the expression of TAZ in tumor tissue was high, the expression of TAZ was more likely to be low expression. The results of factor COX regression model showed that the high expression of tadz and the low expression of LatS2 were observed. The positive lymph node metastasis and tumor diameter over 5 cm were independent factors influencing the poor prognosis of esophageal squamous cell carcinoma. According to the above results, we believe that TAZ is a bad prognostic factor in esophageal squamous cell carcinoma. Lats2 is a good prognostic factor in esophageal squamous cell carcinoma, both of which may play a role in the progression, invasion and metastasis of esophageal squamous cell carcinoma, and may be used as a prognostic marker.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.1

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本文編號(hào)：1496271