RUNX3在肾癌中的表达及临床意义的研究

发布时间：2018-07-24 08:41

【摘要】：研究背景肾癌是我国成人泌尿系统第二常见的恶性肿瘤,其发病率与死亡率占全身恶性肿瘤的2%。早期局限性肾癌以外科手术为主要的治疗手段,然而晚期转移性肾癌因对放、化疗不敏感使得晚期肾癌的预后不甚乐观。目前生物免疫治疗与靶向治疗成为晚期肾癌的主要治疗措施,在临床疗效方面虽然取得了显著的进步,但大部分患者无法获得满意的完全缓解率及肿瘤无进展生存期,故研究开发新的肾癌靶点及癌症通路成为临床迫切待解决的问题。人源性RUNT相关转录因子3(RUNX3)是RUNT家族的核心成员,RUNX3基因作为转录生长-β(TGF-β)信号转导通路下的一个信号因子,通过促进肿瘤细胞凋亡参与调控肿瘤细胞的增殖、死亡、血管生成及侵袭。目前大量的研究表明RUNX3基因作为一个抑癌基因其失活、突变与缺失与胃癌、结肠癌、乳腺癌、胰腺癌等肿瘤的发生有密切关系。另有少数报道称在一部分头颈部肿瘤及黑色素瘤中存在高表达现象,提示RUNX3可能具有致癌作用。研究目的基于以上情况,本文初步研究了 RUNX3在肾癌及癌旁组织中的表达差异,并通过文献查阅对其机制进行了初步的探索,并研究了该因子的表达与临床预后的关系。实验方法收集了 2014年10月至2015年9月于山东大学齐鲁医院泌尿外科一区行20例行肾癌根治术患者肾透明细胞癌癌组织及对应的癌旁组织,组织切取后立即放入液氮罐中保存,并把标本转入-80摄氏度冰箱中保存。所有癌症标本均经过山东大学齐鲁医院病理科证实为肾透明细胞癌。随后将切取的新鲜冰冻组织行Western-blot、实时荧光定量PCR实验和免疫组化染色,分别从蛋白质水平和mRNA水平检测这20对组织中RUNX3的表达差异。并将RUNX3的表达与临床病理资料相结合,分析其相关性。实验结果1.Western-blot结果显示,相对于癌旁组织,肾癌组织中的RUNX3成明显的高表达。2.免疫组织化学染色结果显示,在肾癌组织中RUNX3作为转录因子在肾癌细胞核中表达,并且癌组织中的表达明显高于癌旁组织。3.RT-PCR结果与Western-blot结果一致,肾癌组织的RUNX3 mRNA表达明显高于癌旁组织。实验结论RUNX3在肾癌组织中的表达高于正常的癌旁组织。RUNX3作为经典的抑癌基因具有潜在的致癌作用,其在肾癌中的致癌机制有待进一步研究。
[Abstract]:Background Renal cell carcinoma (RCC) is the second most common malignant tumor in adult urinary system in China. Surgical treatment is the main treatment for early localized renal cell carcinoma. However, the prognosis of advanced metastatic renal cell carcinoma is not optimistic because of its insensitivity to radiotherapy and chemotherapy. At present, biological immunotherapy and targeted therapy have become the main treatment measures for advanced renal cell carcinoma. Although significant progress has been made in clinical efficacy, most patients can not obtain satisfactory complete remission rate and progression free survival. Therefore, the research and development of new renal cell carcinoma targets and cancer pathway has become an urgent clinical problem to be solved. Human RUNT related transcription factor 3 (RUNX3) is a key member of the RUNT family, RUNX3 gene, as a signal factor of transcriptional growth-尾 (TGF- 尾) signal transduction pathway, involved in the regulation of tumor cell proliferation and death by promoting apoptosis of tumor cells. Angiogenesis and invasion. A large number of studies have shown that the inactivation of RUNX3 gene as a tumor suppressor gene, mutation and deletion are closely related to the occurrence of gastric cancer, colon cancer, breast cancer, pancreatic cancer and other tumors. There are also few reports of overexpression in some head and neck tumors and melanoma suggesting that RUNX3 may be carcinogenic. Objective to investigate the difference of RUNX3 expression in renal cell carcinoma and paracancerous tissues, and to explore its mechanism by literature review, and to study the relationship between the expression of RUNX3 and clinical prognosis. Methods from October 2014 to September 2015, 20 cases of renal clear cell carcinoma (RCC) and their adjacent tissues were collected and stored in a liquid nitrogen tank in Urology, Qilu Hospital, Shandong University from October 2014 to September 2015. The specimens are stored in-80 degrees Celsius refrigerator. All cancer specimens were confirmed as renal clear cell carcinoma by the Department of Pathology of Qilu Hospital, Shandong University. The fresh frozen tissues were then detected by Western-blot, real-time fluorescence quantitative PCR assay and immunohistochemical staining. The difference of RUNX3 expression in the 20 pairs of tissues was detected from protein level and mRNA level, respectively. The correlation between RUNX3 expression and clinicopathological data was analyzed. The results of 1.Western-blot showed that the expression of RUNX3 in renal cell carcinoma was significantly higher than that in paracancerous tissues. Immunohistochemical staining showed that RUNX3 was expressed in the nucleus of RCC as a transcription factor, and the expression of RUNX3 in RCC was significantly higher than that in paracancerous tissue. 3. RT-PCR results were consistent with Western-blot results. The expression of RUNX3 mRNA in renal carcinoma tissues was significantly higher than that in paracancerous tissues. Conclusion the expression of RUNX3 in renal cell carcinoma is higher than that in normal paracancerous tissue. RUNX3 as a classical tumor suppressor gene has a potential carcinogenic effect. The carcinogenic mechanism of RUNX3 in renal cell carcinoma needs further study.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.11

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