LXRβ在皮肤鳞状细胞癌中的表达及意义

发布时间：2019-04-20 09:36

【摘要】：背景皮肤鳞状细胞癌(Cutaneous squamous cell carcinoma,c SCC)是一种发病率仅次于基底细胞癌的非黑色素瘤性皮肤恶性肿瘤,主要来源于皮肤表皮或附属器角质形成细胞[1]。近年来研究发现,随着人口老龄化速度加快和环境污染等原因,皮肤鳞状细胞癌的发病率也日益升高。皮肤鳞状细胞癌好发于头面颈部等曝光部位,但起病初期由于患者重视程度不够,延误了最佳的治疗时期,待其病情进展较快时,往往皮损较大,浸润较深,甚至发生了远处转移,手术切除难度较大,治疗困难,预后较差。因此,皮肤鳞状细胞癌不仅影响患者美观,还可能导致毁容,甚至威胁患者生命。近年来,越来越多的研究者发现,许多肿瘤中脂类代谢相关基因的异常表达和肿瘤的发生、发展密切相关。其中,作为脂质合成和代谢的关键调节因子,肝X受体(Liver X receptors,LXRs)及其下游基因参与了肿瘤的脂质代谢,通过影响肿瘤的微环境进而对肿瘤细胞的增殖和凋亡起到调控作用[2,3]。我们前期研究发现,LXRs在人角质形成细胞和皮肤鳞癌细胞系中存在差异性表达,其中LXRβ表达明显高于LXRα。然而,这种表达差异是否与皮肤鳞状细胞癌的发生、发展有关,目前尚无文献报道。为此,本研究通过观察皮肤正常角质形成细胞(Keratinocyte,KC)与皮肤鳞癌A431细胞中LXRβ的表达情况,分析其在皮肤鳞状细胞癌疾病进展过程中的变化规律和LXRβ与皮肤鳞状细胞癌临床病理参数之间的关系,初步探讨LXR在皮肤鳞状细胞癌发生和发展过程中的作用。目的观察在角质形成细胞和皮肤鳞癌A431细胞中LXRs的m RNA和蛋白表达情况,比较LXRβ在正常皮肤(NS)、日光性角化病(AK)、鲍恩病(BD)、皮肤鳞状细胞癌(c SCC)中的表达及分布情况,旨在加深对LXRβ在皮肤鳞状细胞癌发病机制中的作用的理解。方法1.采用PCR array检测LXRs在角质形成细胞和皮肤鳞癌A431细胞中m RNA的表达水平。2.采用Western blot检测LXRs在角质形成细胞和皮肤鳞癌A431细胞中蛋白表达水平。3.采用免疫组化Envision法检测LXRβ在40例正常皮肤(NS)、52例日光性角化病(AK)、40例鲍恩病(BD)、60例皮肤鳞状细胞癌(c SCC)中的表达,分析LXRβ的表达与患者各临床参数之间的关系。结果1.PCR array结果显示,LXRs在人角质形成细胞和皮肤鳞癌A431细胞中存在差异性表达。与角质形成细胞相比,皮肤鳞癌A431细胞系中LXRα、LXRβ的m RNA表达水平均升高,但以LXRβ升高更为明显。2.Western Blot检测发现,LXRs在角质形成细胞和皮肤鳞癌A431细胞中均有表达,与角质形成细胞相比,皮肤鳞癌A431细胞中LXRα、LXRβ的蛋白表达水平升高,其中LXRβ为优势表达亚型。3.免疫组化结果表明,LXRβ在正常皮肤、日光性角化病、鲍恩病、皮肤鳞状细胞癌中表达依次升高,以皮肤鳞状细胞癌升高最为明显。分析LXRβ的表达与皮肤鳞状细胞癌临床病理参数的关系时发现:LXRβ的表达与皮肤鳞状细胞癌浸润深度、肿瘤大小、分化程度相关(P0.05);与年龄、性别、曝光部位无明显相关性(P0.05)。结论1.LXRs在皮肤鳞癌A431细胞中的表达显著高于在角质形成细胞中的表达,LXRβ为优势表达亚型。2.LXRβ在皮肤鳞癌A431细胞和皮肤鳞癌组织中的表达均升高。其中LXRβ在正常皮肤、日光性角化病、鲍恩病及皮肤鳞状细胞癌中的表达水平依次升高,提示LXRβ在皮肤鳞状细胞癌的发生、发展过程中可能参与了肿瘤的增殖和分化。3.在不同分化程度的皮肤鳞状细胞癌中,LXRβ在原位癌(鲍恩病)、高、中分化鳞状细胞癌中的表达高于低分化鳞状细胞癌。我们推测LXRs可能参与了皮肤鳞状细胞癌的发生和发展过程。
[Abstract]:Background: Cutaneous squamous cell carcinoma (c-SCC) is a non-melanoma skin malignant tumor, which is second only to the basal cell carcinoma, and is mainly derived from the skin epidermis or the attached cutin to form the cell[1]. In recent years, the incidence of squamous cell carcinoma of the skin is also increasing with the speed of the aging of the population and the environmental pollution. The skin squamous cell carcinoma is good at the exposure sites such as the neck of the head and the like, but at the early stage of the disease, due to the insufficient attention degree of the patient, the optimal treatment period is delayed, The treatment is difficult and the prognosis is poor. Therefore, squamous cell carcinoma of the skin not only affects the beauty of the patient, but also can lead to disfigurement, and even the life of the patient. In recent years, more and more researchers have found that the abnormal expression of lipid metabolism-related genes in many tumors is closely related to the occurrence and development of the tumor. Among them, as a key regulatory factor for lipid synthesis and metabolism, the liver X receptor (LXRs) and its downstream genes are involved in the lipid metabolism of the tumor, and the microenvironment of the tumor can be used to control the proliferation and apoptosis of the tumor cells[2,3]. In our earlier study, the expression of LXRs in human keratinocytes and squamous cell carcinoma cell lines was found to be different, and the expression of LXR was significantly higher than that of LXR. However, this difference is related to the occurrence and development of squamous cell carcinoma of the skin, and there is no literature report. To this end, by observing the expression of LXR in the skin squamous cell carcinoma A431 cells by observing the expression of LXR in the skin squamous cell carcinoma A431 cells, the relationship between the change rule of the skin squamous cell carcinoma and the clinicopathological parameters of the LXR antigen and the squamous cell carcinoma of the skin is analyzed, The role of LXR in the development and development of squamous cell carcinoma of the skin was discussed. Objective To observe the expression and distribution of mRNA and protein of LXRs in keratinocytes and skin squamous cell carcinoma A431 cells, and to compare the expression and distribution of LXR in normal skin (NS), solar keratosis (AK), Bowen's disease (BD) and skin squamous cell carcinoma (c SCC). To improve the understanding of the role of LXR in the pathogenesis of skin squamous cell carcinoma. Method 1. The expression level of m-RNA of LXRs in keratinocytes and squamous cell carcinoma A431 cells was detected by PCR-array. Western blot was used to detect the level of protein expression of LXRs in keratinocytes and squamous cell carcinoma A431 cells. The expression of LXR antigen in 40 normal skin (NS),52 cases of solar keratosis (AK),40 cases of Bowen's disease (BD) and 60 cases of skin squamous cell carcinoma (c SCC) was detected by immunohistochemical method. The relationship between the expression of LXR antigen and the clinical parameters of the patient was analyzed. Results 1. The results showed that the expression of LXRs in human keratinocytes and skin squamous cell carcinoma A431 cells was different. Compared with the keratinocytes, the expression of mRNA of LXR and LXR in the skin squamous cell carcinoma A431 cell line increased, but it was more obvious with the increase of LXR.2. Western Blot detection showed that the LXRs were expressed in both the keratinocytes and the skin squamous cell carcinoma A431 cells, compared with the keratinocytes. The expression level of LXR and LXR in the A431 cells of squamous cell carcinoma of the skin was increased, and the LXR gene was the dominant expression subtype. The results showed that the expression of LXR in the normal skin, the solar keratosis, the Bowen's disease and the squamous cell carcinoma of the skin increased in sequence, and the increase of the squamous cell carcinoma of the skin was the most obvious. The relationship between the expression of LXR antigen and the clinicopathological parameters of squamous cell carcinoma of the skin was analyzed. The expression of LXR gene was related to the invasion depth of squamous cell carcinoma of the skin, the size of the tumor and the degree of differentiation (P0.05), and there was no significant correlation with age, sex and exposure (P0.05). Conclusion 1. The expression of LXRs in the skin squamous cell carcinoma A431 cells is significantly higher than that in the keratinocytes. The expression of LXR in the normal skin, the solar keratosis, the Bowen's disease and the squamous cell carcinoma of the skin was increased in turn, suggesting that the LXR gene might be involved in the proliferation and differentiation of the tumor during the development of the squamous cell carcinoma of the skin. The expression of LXR in squamous cell carcinoma of the skin with different degree of differentiation is higher than that of low-differentiated squamous cell carcinoma. We assume that LXRs may be involved in the occurrence and development of squamous cell carcinoma of the skin.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.5

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