TAZ和Lats2在食管鳞癌组织的表达及临床意义

发布时间：2018-02-08 21:05

本文关键词： 食管鳞癌 TAZ Lats2 免疫组化　出处：《第二军医大学》2017年硕士论文　论文类型：学位论文

【摘要】：食管癌为全球范围内发病率第八位的恶性肿瘤,并占因肿瘤死亡的第六位。中国是食管癌的高发国家,食管癌在我国是第四大恶性肿瘤,食管癌90%以上病理类型为鳞状细胞癌。食管鳞癌的早期症状隐匿,进展迅速,且治疗手段较为局限,诊治过程中存在较多难题,尤其在分子层面上,该疾病的预后标志物目前仍在探索中。对相应肿瘤分子标志物的探索,在优化食管鳞癌的个体化治疗,以及对该类疾病患者的预后评估过程中,具有重要意义。具有PDZ模序的转录共激活因子(transcriptional coactivator with PDZ binding motif,TAZ)是一类癌基因,是Hippo通路的主要效应因子,在调控组织器官大小形状,调节细胞生长及接触性抑制的机制中发挥作用。研究发现TAZ在多类肿瘤组织内的表达增高,并在肿瘤疾病的发生及发展过程中发挥作用。TAZ通过在细胞核内与转录激活因子结合后,可激活基因转录,刺激细胞增殖及侵袭转移,并介导肿瘤细胞的干细胞分化过程。大肿瘤抑制因子2(large tumorsuppressor kinase 2,Lats2)为拉特抑癌家族(Lats Family)成员之一,通过调控细胞周期检查点(G1/S)阻滞细胞的有丝分裂。研究发现,Lats2在多种肿瘤组织内表达下调,并在肿瘤的发生发展中起抑癌作用。与TAZ一样,Lats2也为Hippo通路的组成元件,并为位于TAZ上游的负向控制基因,通过磷酸化后者使其失去转录共激活活性。此外,Lats2可参与影响其他通路(如EGFR信号通路、Wnt通路、P53通路等)发挥其抑癌功能。本次研究通过免疫组化(MaxVision法)观察食管鳞癌组织内TAZ和Lats2的表达情况及相互关系,并分析其对食管鳞癌患者临床病理特征及预后的关系。TAZ的高表达与肿瘤的浸润深度、淋巴结转移阳性、分化程度较低、较大的肿瘤直径及较晚的肿瘤分期具有相关性(p0.05),TAZ表达高者,食管鳞癌患者预后较差。Lats2的表达水平与患者淋巴结转移、组织分化程度及肿瘤分期相关,Lats2表达高者,预示着较少的淋巴结转移可能、较高的分化程度和较早的分期(p0.05)。在生存期的研究中发现,肿瘤组织内Lats2表达高者较Lats2表达低者具有更长的生存期。相关性分析结果提示TAZ与Lats2的表达存在负相关性(p0.001),即当肿瘤组织内TAZ为高表达时,Lats2更倾向于低表达。多因素COX回归模型结果显示,TAZ高表达、Lats2低表达、淋巴结转移阳性及肿瘤直径超过5cm均为食管鳞癌患者不良预后的独立影响因子。根据上述研究结果,我们认为在食管鳞癌中,TAZ是食管鳞癌患者预后不良的影响因子,而Lats2是食管鳞癌患者预后良好的影响因子,二者都可能在肿瘤的进展及侵袭转移中起到一定作用,并有望作为预后评估的标志物。
[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.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.1

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