Runx3，Smad4及Ki-67蛋白在皮肤恶性黑色素瘤中的表达和意义

发布时间：2018-05-19 22:14

本文选题：皮肤恶性黑色素瘤 + Runt3　；参考：《郑州大学》2010年硕士论文

【摘要】： 目的皮肤恶性黑色素瘤(cutaneous malignant melanoma, CMM)是一种恶性程度极高的皮肤肿瘤,细胞无限增殖与凋亡抑制是其主要发病机制。目前对CMM尚无完全有效的预防与治疗措施。国内外对于CMM发生机制的研究已经取得了较大的进步。研究表明,CMM是正常细胞染色体多重损伤的复杂过程,它的发生、发展以及转归的研究涉及了癌基因的激活、抑癌基因的失活、凋亡基因紊乱、DNA转录表达失控等。人类runt相关转录因子3(runt-related transcription factor 3 gene, Runx3)作为一种抑癌基因,其蛋白可指导转化生长因子-β(transforming growth factor-β, TGF-β)信号转导过程中激活的Smad复合物从细胞质内转入细胞核内的特定靶位点,加强Smad复合物与靶位点的结合强度并激活靶基因,从而对细胞的分化、细胞周期调控、凋亡和恶性转化起作用。Ki-67是与增殖细胞相关的核抗原。本实验通过检测Runx3、Smad4及Ki-67蛋白在CMM中的表达水平并分析它们之间的相互关系,从细胞增殖和凋亡方面探讨Runx3、Smad4及Ki-67对CMM发生发展所起的作用。材料与方法本研究选用郑州大学第一附属医院病理科2006年7月～2008年12月切除且病历资料完整、病理诊断明确的CMM38例及皮肤交界痣20例；所有患者均无合并皮肤病、结缔组织病、免疫系统疾病及其他重要脏器疾病；患者术前均未进行放疗、化疗、免疫、冷冻、激光及其他治疗。20例正常皮肤组织(对照组)为郑州大学第一附属医院整形外科非癌及未合并皮肤病的患者行全厚皮片移植时修剪所剩全厚皮片与美容手术者切除的多余全厚皮肤。运用免疫组织化学SP法,探讨在CMM中Runx3, Smad4和与细胞增殖相关的Ki-67之间的关系。统计方法采用SPSS13.0软件对数据进行处理,运用卡方检验和相关性分析,检验标准α=0.05,X2分割检验标准α’=0.0167。结果 1.Runx3蛋白主要表达于黑色素细胞的细胞核,在CMM中低表达。在CMM中其阳性表达率为23.68%(9／38),与皮肤交界痣80%(16／20)、正常皮肤90%(18／20)相比差异具有统计学意义(P0.0167),皮肤交界痣与正常皮肤相比差异无统计学意义(P0.0167) 2.Smad4蛋白主要表达于黑色素细胞的细胞质,在CMM中低表达。在CMM中其阳性表达率为34.21%(13／38),与皮肤交界痣85%(17／20)、正常皮肤95%(19／20)相比差异具有统计学意义(P0.0167),皮肤交界痣与正常皮肤相比差异无统计学意义(P0.0167)。 3.Ki-67蛋白主要表达于黑色素细胞即增殖细胞的细胞核。在CMM中其阳性表达率为78.95%(30／38),与皮肤交界痣30.00%(6／20)、正常皮肤25%(5／20)相比差异具有统计学意义(P0.0167),皮肤交界痣与正常皮肤相比差异无统计学意义(P0.0167)。 4.相关性分析显示,Runx3、Smad4蛋白表达与细胞增殖核抗原Ki-67蛋白表达呈负相关(P0.05),Runx3与Smad4蛋白表达呈正相关(r=0.455)。结论 1.Runx3与Smad4蛋白在CMM黑色素细胞中的表达明显较皮肤交界痣及正常皮肤低,它们的低表达可能通过某种细胞信号转导途径促进黑色素细胞的增殖,抑制黑色素细胞的凋亡,从而促进CMM的形成与发展。提示它们在CMM中可能起抑癌作用。 2.Smad4参与的TGF-β信号转导途径最终作用是促进细胞凋亡,抑制细胞增殖。Runx3是其上游的作用分子,在CMM中其蛋白低表达可阻碍该信号途径的顺利进行,从而促进CMM的发展。 3.Ki-67是一种细胞增殖核抗原,在CMM中可反映黑色素细胞的增殖活性,为CMM的发展程度和预后提供可靠的分子依据。
[Abstract]:objective
Cutaneous malignant melanoma (CMM) is a highly malignant skin tumor. Cell proliferation and inhibition of apoptosis are its main pathogenesis. There is no effective prevention and treatment for CMM at present.
The research on the mechanism of CMM has made great progress both at home and abroad. Research has shown that CMM is a complex process of multiple damage of normal cell chromosomes. Its occurrence, development and transformation involve the activation of oncogenes, inactivation of tumor suppressor genes, the disorder of apoptotic genes, and out of control of DNA transcriptional expression. Human runt related transcriptional causes Sub3 (runt-related transcription factor 3 gene, Runx3) is a tumor suppressor gene whose protein can guide the specific target site of the Smad complex activated by the transforming growth factor beta (transforming growth factor- beta, TGF- beta) signal transduction process from the cytoplasm to the nucleus, and strengthens the binding strength of the Smad complex and the target site. The target gene is activated and.Ki-67 is the nuclear antigen associated with cell proliferation, cell cycle regulation, apoptosis and malignant transformation. In this experiment, the expression level of Runx3, Smad4 and Ki-67 protein in CMM was detected and the relationship between them was analyzed, and Runx3, Smad4 and Ki-67 were discussed from cell proliferation and apoptosis. The role of the development of CMM.
Materials and methods
In this study, 20 cases of CMM38 and 20 cases of skin borderline nevus of the pathology department of the First Affiliated Hospital of Zhengzhou University were excised from July 2006 to December 2008. All patients had no dermatosis, connective tissue disease, immune system disease and other important visceral diseases. The patients were not treated with radiotherapy and chemotherapy before operation. Immunization, cryopreservation, laser and other treatment of.20 normal skin tissue (control group) for patients with non cancer and unincorporated skin diseases in the First Affiliated Hospital of Zhengzhou University, the excess thick skin was trimmed with all thick skin slices and cosmetic surgery patients during full thickness skin graft. Immunohistochemical SP method was used to explore Runx3, Sm in CMM. The relationship between Ad4 and Ki-67 related to cell proliferation. The statistical method uses SPSS13.0 software to deal with the data, using chi square test and correlation analysis to test the standard alpha =0.05, X2 segmentation test standard alpha =0.0167.
Result
1.Runx3 protein was mainly expressed in the nucleus of melanocytes and low expression in CMM. The positive expression rate in CMM was 23.68% (9 / 38). Compared with the skin borderline nevus 80% (16 / 20) and normal skin 90% (18 / 20), the difference was statistically significant (P0.0167). There was no statistical difference between the skin borderline nevus and the normal skin (P0.0167).
The expression of 2.Smad4 protein was mainly expressed in the cytoplasm of melanocytes and low expression in CMM. The positive expression rate in CMM was 34.21% (13 / 38). Compared with the skin borderline nevus 85% (17 / 20) and normal skin 95% (19 / 20), the difference was statistically significant (P0.0167). There was no statistical difference between the skin borderline nevus and the normal skin (P0.0167).
3.Ki-67 protein was mainly expressed in the nucleus of melanocytes, the proliferating cell, and the positive expression rate in CMM was 78.95% (30 / 38). Compared with the skin borderline nevus 30% (6 / 20) and the normal skin 25% (5 / 20), the difference was statistically significant (P0.0167). There was no statistical difference between the skin borderline nevus and the normal skin (P0.0167).
4. correlation analysis showed that Runx3, Smad4 protein expression was negatively correlated with Ki-67 protein expression of cell proliferation nuclear antigen (P0.05), and Runx3 was positively correlated with the expression of Smad4 protein (r=0.455).
conclusion
The expression of 1.Runx3 and Smad4 protein in CMM melanocytes is obviously lower than that of skin borderline nevus and normal skin. Their low expression may promote the proliferation of melanocytes through some cell signal transduction pathway, inhibit the apoptosis of melanocytes and promote the formation and development of CMM, suggesting that they may play a role in inhibiting cancer in CMM.
The final effect of TGF- beta signal transduction pathway involved in 2.Smad4 is to promote cell apoptosis and to inhibit cell proliferation,.Runx3 is the upstream molecule. The low expression of protein in CMM can impede the smooth progress of the signal pathway, thus promoting the development of CMM.
3.Ki-67 is a proliferating cell nuclear antigen, which can reflect the proliferative activity of melanocytes in CMM, and provide reliable molecular basis for the development and prognosis of CMM.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R739.5

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