【摘要】：背景皮膚鱗狀細(xì)胞癌(Cutaneous squamous cell carcinoma,c SCC)是一種發(fā)病率僅次于基底細(xì)胞癌的非黑色素瘤性皮膚惡性腫瘤,主要來(lái)源于皮膚表皮或附屬器角質(zhì)形成細(xì)胞[1]。近年來(lái)研究發(fā)現(xiàn),隨著人口老齡化速度加快和環(huán)境污染等原因,皮膚鱗狀細(xì)胞癌的發(fā)病率也日益升高。皮膚鱗狀細(xì)胞癌好發(fā)于頭面頸部等曝光部位,但起病初期由于患者重視程度不夠,延誤了最佳的治療時(shí)期,待其病情進(jìn)展較快時(shí),往往皮損較大,浸潤(rùn)較深,甚至發(fā)生了遠(yuǎn)處轉(zhuǎn)移,手術(shù)切除難度較大,治療困難,預(yù)后較差。因此,皮膚鱗狀細(xì)胞癌不僅影響患者美觀,還可能導(dǎo)致毀容,甚至威脅患者生命。近年來(lái),越來(lái)越多的研究者發(fā)現(xiàn),許多腫瘤中脂類代謝相關(guān)基因的異常表達(dá)和腫瘤的發(fā)生、發(fā)展密切相關(guān)。其中,作為脂質(zhì)合成和代謝的關(guān)鍵調(diào)節(jié)因子,肝X受體(Liver X receptors,LXRs)及其下游基因參與了腫瘤的脂質(zhì)代謝,通過(guò)影響腫瘤的微環(huán)境進(jìn)而對(duì)腫瘤細(xì)胞的增殖和凋亡起到調(diào)控作用[2,3]。我們前期研究發(fā)現(xiàn),LXRs在人角質(zhì)形成細(xì)胞和皮膚鱗癌細(xì)胞系中存在差異性表達(dá),其中LXRβ表達(dá)明顯高于LXRα。然而,這種表達(dá)差異是否與皮膚鱗狀細(xì)胞癌的發(fā)生、發(fā)展有關(guān),目前尚無(wú)文獻(xiàn)報(bào)道。為此,本研究通過(guò)觀察皮膚正常角質(zhì)形成細(xì)胞(Keratinocyte,KC)與皮膚鱗癌A431細(xì)胞中LXRβ的表達(dá)情況,分析其在皮膚鱗狀細(xì)胞癌疾病進(jìn)展過(guò)程中的變化規(guī)律和LXRβ與皮膚鱗狀細(xì)胞癌臨床病理參數(shù)之間的關(guān)系,初步探討LXR在皮膚鱗狀細(xì)胞癌發(fā)生和發(fā)展過(guò)程中的作用。目的觀察在角質(zhì)形成細(xì)胞和皮膚鱗癌A431細(xì)胞中LXRs的m RNA和蛋白表達(dá)情況,比較LXRβ在正常皮膚(NS)、日光性角化病(AK)、鮑恩病(BD)、皮膚鱗狀細(xì)胞癌(c SCC)中的表達(dá)及分布情況,旨在加深對(duì)LXRβ在皮膚鱗狀細(xì)胞癌發(fā)病機(jī)制中的作用的理解。方法1.采用PCR array檢測(cè)LXRs在角質(zhì)形成細(xì)胞和皮膚鱗癌A431細(xì)胞中m RNA的表達(dá)水平。2.采用Western blot檢測(cè)LXRs在角質(zhì)形成細(xì)胞和皮膚鱗癌A431細(xì)胞中蛋白表達(dá)水平。3.采用免疫組化Envision法檢測(cè)LXRβ在40例正常皮膚(NS)、52例日光性角化病(AK)、40例鮑恩病(BD)、60例皮膚鱗狀細(xì)胞癌(c SCC)中的表達(dá),分析LXRβ的表達(dá)與患者各臨床參數(shù)之間的關(guān)系。結(jié)果1.PCR array結(jié)果顯示,LXRs在人角質(zhì)形成細(xì)胞和皮膚鱗癌A431細(xì)胞中存在差異性表達(dá)。與角質(zhì)形成細(xì)胞相比,皮膚鱗癌A431細(xì)胞系中LXRα、LXRβ的m RNA表達(dá)水平均升高,但以LXRβ升高更為明顯。2.Western Blot檢測(cè)發(fā)現(xiàn),LXRs在角質(zhì)形成細(xì)胞和皮膚鱗癌A431細(xì)胞中均有表達(dá),與角質(zhì)形成細(xì)胞相比,皮膚鱗癌A431細(xì)胞中LXRα、LXRβ的蛋白表達(dá)水平升高,其中LXRβ為優(yōu)勢(shì)表達(dá)亞型。3.免疫組化結(jié)果表明,LXRβ在正常皮膚、日光性角化病、鮑恩病、皮膚鱗狀細(xì)胞癌中表達(dá)依次升高,以皮膚鱗狀細(xì)胞癌升高最為明顯。分析LXRβ的表達(dá)與皮膚鱗狀細(xì)胞癌臨床病理參數(shù)的關(guān)系時(shí)發(fā)現(xiàn):LXRβ的表達(dá)與皮膚鱗狀細(xì)胞癌浸潤(rùn)深度、腫瘤大小、分化程度相關(guān)(P0.05);與年齡、性別、曝光部位無(wú)明顯相關(guān)性(P0.05)。結(jié)論1.LXRs在皮膚鱗癌A431細(xì)胞中的表達(dá)顯著高于在角質(zhì)形成細(xì)胞中的表達(dá),LXRβ為優(yōu)勢(shì)表達(dá)亞型。2.LXRβ在皮膚鱗癌A431細(xì)胞和皮膚鱗癌組織中的表達(dá)均升高。其中LXRβ在正常皮膚、日光性角化病、鮑恩病及皮膚鱗狀細(xì)胞癌中的表達(dá)水平依次升高,提示LXRβ在皮膚鱗狀細(xì)胞癌的發(fā)生、發(fā)展過(guò)程中可能參與了腫瘤的增殖和分化。3.在不同分化程度的皮膚鱗狀細(xì)胞癌中,LXRβ在原位癌(鮑恩病)、高、中分化鱗狀細(xì)胞癌中的表達(dá)高于低分化鱗狀細(xì)胞癌。我們推測(cè)LXRs可能參與了皮膚鱗狀細(xì)胞癌的發(fā)生和發(fā)展過(guò)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.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R739.5

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