RKIP在喉鳞癌中的表达及意义

发布时间：2018-11-13 11:52

【摘要】： 目的:喉癌(laryngeal cancer)是来源于喉黏膜上皮组织的恶性肿瘤,是头颈部常见的恶性肿瘤,发病率较高。其病因可能与吸烟、饮酒、空气污染、职业因素、病毒感染、放射线等有关。近年来喉癌的发病率有日益增多的趋势。喉癌的治疗方式主要有手术、放疗等,早期喉癌的治疗效果好,晚期喉癌疗效较差。喉癌发生转移是引起病人死亡和治疗失败的主要原因。Raf-1激酶抑制蛋白(Raf-1 kinase inhibitor protein, RKIP )广泛存在于人体的许多组织中,如:睾丸、肾上腺、肝、肾等。RKIP家族成员在序列上有高度的相似性,在人体中发挥重要的保守的生物学功能。最近,在对前列腺癌、结直肠癌、乳腺癌、恶性黑素瘤等的研究中,发现RKIP能够抑制肿瘤细胞转移,因此它被认为是一种肿瘤转移抑制基因,在恶性肿瘤的发展和预后中具有重要的作用。对于RKIP抑制肿瘤转移的机制现尚不清楚,在体内,RKIP参与许多信号通路的调节,发挥重要作用。如RKIP通过与Raf-1相互作用从而抑制丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)信号通路的活性。我们知道MAPK信号通路参与调节细胞的许多主要功能,如:增殖、分化及凋亡。在30%的肿瘤中该通路发生改变,并在致癌性转变、侵袭和转移中发挥重要作用。该通路是通过Raf-1/MAPK激酶/细胞外信号调节激酶(extracellular signal-regulated kinase, ERK)三个激酶的级联反应来发挥作用的,Raf-1磷酸化后激活MAPK激酶,MAPK激酶磷酸化后进一步激活ERK,最后一级的ERK磷酸化后发挥作用。本研究探讨Raf-1激酶抑制蛋白在喉鳞癌组织、淋巴结转移灶及正常喉鳞状上皮中的表达及其临床意义。同时检测磷酸化的ERK (phospho-extracellular signal-regulated kinase, P-ERK)来验证在喉癌中RKIP是否通过MAPK通路发挥抑制喉癌转移的作用。 方法:材料来源于白求恩国际和平医院2007年1月-2009年2月喉癌住院手术患者41例,这些患者术前均未进行化学治疗和放射治疗,所有病例临床资料完整。采用免疫组化方法(PV法)检测41例喉癌患者喉鳞癌组织、淋巴结转移灶及正常喉黏膜中RKIP的表达情况。采用免疫组化方法(SP法)检测41例喉癌患者喉鳞癌组织、淋巴结转移灶及正常喉黏膜中P-ERK的表达情况。 结果: 1 RKIP的表达 1.1在正常喉黏膜的鳞状上皮中,RKIP主要分布于棘细胞及颗粒细胞层,而在基底层中表达阴性。在高分化的肿瘤中,RKIP主要分布于棘细胞样及颗粒细胞样的肿瘤细胞中,而在基底层样细胞中表达阴性。在低分化的肿瘤中,表达多为阴性。 1.2统计学分析结果显示,喉鳞癌RKIP表达水平较正常喉黏膜组织明显降低,差异有统计学意义(P=0.012)。41例喉鳞癌中,有转移的喉癌中表达阳性率低于无转移的喉癌,RKIP表达存在显著差异(P=0.016)。有转移的10例中,原发灶与转移灶相比,RKIP表达无显著差异。RKIP的表达与性别、年龄、肿瘤发病部位、T分期、临床分期等临床病理因素没有直接关系。 2 P-ERK的表达 部分正常黏膜组织中,P-ERK集中分布于基底层和靠近基底层的棘细胞层中。在喉癌中多呈阳性或强阳性表达。 3 RKIP与P-ERK相关性分析 在41例喉癌原发灶标本中,RKIP与P-ERK的表达情况作Spearman秩相关分析,结果P=0.003,r=0.456,有统计学意义,可以认为两者呈正相关性。 结论: 1与正常喉黏膜组织相比,喉鳞癌RKIP表达明显降低。 2 RKIP低表达的喉癌更容易发生转移。 3 RKIP的表达与性别、年龄、肿瘤发病部位、T分期、临床分期等临床病理因素没有直接关系。 4除了通过调节MAPK通路外,RKIP可能通过执行其它未知功能来抑制喉癌转移的发生。
[Abstract]:Objective: Laryngeal cer is a malignant tumor derived from the epithelial tissue of the laryngeal mucosa. It is a common malignant tumor of the head and neck. The etiology may be related to smoking, drinking, air pollution, occupational factors, viral infections, radiation, and the like. In recent years, the incidence of laryngeal cancer is increasing. The treatment of laryngeal carcinoma mainly includes operation, radiotherapy and so on, the treatment effect of the early laryngeal carcinoma is good, and the curative effect of the advanced laryngeal carcinoma is poor. The metastasis of the laryngeal carcinoma is the main cause of the death and failure of the patient. Raf-1 kinase inhibitor protein (RKIP) is widely present in many tissues of human body, such as testis, adrenal gland, liver, kidney, etc. The members of the RKIP family have a high degree of similarity in the sequence and play an important and conservative biological function in the human body. Recently, in the study of prostate cancer, colorectal cancer, breast cancer, and malignant melanoma, it is found that RKIP can inhibit the metastasis of tumor cells, so it is considered to be a tumor metastasis suppressor gene, which plays an important role in the development and prognosis of malignant tumors. The mechanism of RKIP to inhibit tumor metastasis is not clear, and in vivo, RKIP plays an important role in the regulation of many signal pathways. RKIP can inhibit the activity of mitogen-activated protein kinase (MAPK) signaling pathway by interacting with Raf-1. We know that MAPK signaling pathway is involved in the regulation of many major functions of the cell, such as proliferation, differentiation and apoptosis. This pathway changes in 30% of the tumors and plays an important role in the carcinogenicity transition, invasion and metastasis. The pathway is a function of the cascade of three kinases of the extracellular signal-regulated kinase (ERK) through the Raf-1/ MAPK kinase/ extracellular signal-regulated kinase (ERK), and after the phosphorylation of Raf-1, the MAPK kinase is activated, and the ERK is further activated after the phosphorylation of the MAPK kinase, and the ERK at the last stage plays a role. The expression and clinical significance of Raf-1 kinase inhibitor in laryngeal squamous cell carcinoma, lymph node metastasis and normal laryngeal squamous epithelium were discussed in this study. Phosphorylated ERK (P-ERK) was also used to verify the role of RKIP in laryngeal carcinoma to inhibit the metastasis of laryngeal carcinoma. Methods: The materials were from the Bethune International Peace Hospital from January 2007 to February 2009. The expression of RKIP in laryngeal squamous cell carcinoma, lymph node metastasis and normal laryngeal mucosa in 41 patients with laryngeal carcinoma was detected by immunohistochemical method (PV method). Expression of P-ERK in laryngeal squamous cell carcinoma, lymph node metastasis and normal laryngeal mucosa in 41 patients with laryngeal carcinoma by immunohistochemistry (SP method) expression condition The expression of 1. 1 RKIP was 1. 1 in the squamous epithelium of normal laryngeal mucosa, RKIP was mainly distributed in the spine. In high-differentiated tumors, RKIP is mainly distributed in the cell-like and granular-like cells. in tumor cell, and in basal cell-like cells The results showed that the expression of RKIP in laryngeal squamous cell carcinoma was significantly lower than that of normal laryngeal mucosa (P = 0.012). In 41 cases of laryngeal squamous cell carcinoma, the positive rate of expression in laryngeal squamous cell carcinoma was lower than that of non-metastatic laryngeal carcinoma. There was a significant difference between the expression of RKIP and the expression of RKIP (P = 0.016). In the case, there was no significant difference in the expression of RKIP compared with the metastatic focus. The expression of RKIP was related to sex, age, and tumor. Site, T staging, clinical the clinical and pathological factors such as stage were not directly related. The expression of P-ERK P-ERK set in normal mucosal tissue a fine band distributed in the base layer and adjacent to the base layer The expression of RKIP and P-ERK in laryngeal carcinoma was analyzed in 41 patients with laryngeal carcinoma, and the expression of RKIP and P-ERK was used as the expression of Spearm. an绉，

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