Tiam1及CD44在肾癌中的表达及其意义

发布时间：2019-05-11 14:44

【摘要】：背景 肾细胞癌（Renal cell carcinoma，RCC），是泌尿系统常见的恶性肿瘤。外科切除器官局限性肿瘤为肾癌提供了一个治愈的机会，但接受手术治疗的患者中约30％将发生远处转移。RCC对放疗化疗均不敏感，而且免疫生物疗法仅在一小部分病例上观察到部分或完全缓解[1,2,3]。目前，肾癌发病的确切机制尚不明确，抑癌基因的失活和癌基因的激活可能发挥重要作用[4]，相关基因产物的检测对肾癌的早期诊断具有重要的临床意义。Tiam1是鸟苷酸转换因子(guanine nucleotideexchange factors，GEFs)家族成员，参与到包括肾癌在内的许多肿瘤的发生和转移过程[5]。研究还发现Tiam1通过与CD44黏附分子相互作用可提高Rac1信号途径和以透明质酸（CD44的受体）的中介或基质金属蛋白酶的中介可促进乳腺癌、结肠癌等瘤细胞侵润及迁移[6,7,8]。因此，Tiam1联合CD44表达更有助于反映细胞的侵袭及转移状态。目的 研究Tiam1、CD44在肾细胞癌组织中的表达情况，探讨Tiam1、CD44在肾细胞癌发生、发展中的作用及其相互关系，以期对肾细胞癌的临床诊断、治疗和预后提供帮助。方法 应用免疫组化方法（S-P法）检测92例临床肾细胞癌组织和20例癌旁正常肾组织中Tiam1、CD44的表达情况及其相互关系，并与肿瘤临床分期、病理分级进行等临床特征进行相关性分析。 结果 1.肾透明细胞癌组织中Tiam l蛋白阳性表达率为75%（69/92）,阳性表现为镜下黄色或棕色细颗粒，以细胞质中表达为主，其表达与肿瘤的临床分期、有无淋巴结转移及远处转移有关，差异有统计学意义（P＜0.05）。其表达与肿瘤大小、年龄、性别无统计学意义(P＞0.05)；对照组的20例正常组织中Tiam1表达水平低，其表达率为15%（3/20）。 2. CD44在肾透明细胞癌组织中表达率为66.3%（61/92），位于细胞膜，阳性表现为镜下褐色细颗粒，，其表达强度与临床病理资料中Tiam1表达相符。对照组的20例正常组织中CD44表达水平低，其表达率为20%（4/20）。 3.经统计学分析，两者在肾癌组织中的表达呈正相关（相关系数r=0.315，χ2=10.14，P0.01）。 结论 1．肾透明细胞癌组织的Tiam1及CD44表达的水平皆与临床分期以及有无淋巴结转移和血管侵润等密切相关，但与患者的年龄、性别，肿瘤大小等无关。 2．肾透明细胞癌组织的Tiaml及CD44的表达水平呈正相关，提示Tiam1与CD44二者的表达在肾细胞癌中可有协同作用，共同促使肿瘤在局部侵袭和淋巴结转移。
[Abstract]:Background Renal cell carcinoma (Renal cell carcinoma,RCC) is a common malignant tumor of urinary system. Surgical resection of localized tumors of the organs provides an opportunity to cure renal cell carcinoma, but about 30% of the patients undergoing surgical treatment will have distant metastasis. RCC is not sensitive to radiotherapy and chemotherapy. And immunobiotherapy observed partial or complete remission in only a small number of cases [1, 2, 3]. At present, the exact mechanism of renal cell carcinoma is not clear, the inactivation of tumor inhibitor gene and the activation of tumor gene may play an important role [4]. The detection of related gene products is of great clinical significance for the early diagnosis of renal cell carcinoma. Tiam1 is a member of the guanylate conversion factor (guanine nucleotideexchange factors,GEFs family and is involved in the occurrence and metastasis of many tumors, including renal cell carcinoma [5]. It was also found that Tiam1 could enhance the Rac1 signal pathway by interacting with CD44 adhesion molecules and promoted the invasion and migration of breast cancer and colon cancer cells mediated by hyaluronic acid (CD44 receptor) or matrix metalloproteinases [6, 7, 8]. Therefore, the expression of Tiam1 combined with CD44 is more helpful to reflect the invasion and metastasis of cells. Objective to study the expression of Tiam1,CD44 in renal cell carcinoma (RCC) and to explore the role of Tiam1,CD44 in the occurrence and development of RCC and its relationship with each other, so as to provide help for clinical diagnosis, treatment and prognosis of RCC. Methods Immunohistochemical method (S 鈮

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