本文選題：脂肪瘤 + 基因芯片��； 參考：《第二軍醫(yī)大學(xué)》2012年博士論文

【摘要】：研究背景 脂肪瘤(lipoma)是由成熟脂肪組織增生而形成的良性腫瘤，既有的大多數(shù)教科書認(rèn)為此病可發(fā)生于任何年齡，但多見于40～60歲的成年人。由于絕大多數(shù)的脂肪瘤不會(huì)惡變，無特殊不適癥狀和并發(fā)癥，易于診斷，治療手段單一（目前多以手術(shù)切除為主），因此，對(duì)脂肪瘤的全面研究未能引起足夠的重視，其研究進(jìn)展也相對(duì)較慢。在臨床工作中，大多數(shù)醫(yī)生會(huì)注意到，對(duì)于單發(fā)脂肪瘤，手術(shù)基本可以治愈，預(yù)后良好，而對(duì)于皮下多發(fā)脂肪瘤患者，此病雖不至于危及生命，但會(huì)使患者終日憂心于腫瘤的不斷進(jìn)展和苦于找不到徹底根治的方法和手段，從而嚴(yán)重影響患者的身心健康和生活質(zhì)量。更為重要的是，隨著社會(huì)飛速進(jìn)步帶來的壓力增大、不良生活習(xí)慣增加及飲食結(jié)構(gòu)的變化，皮下多發(fā)脂肪瘤的發(fā)病率異常增高，門診患者中此類疾病幾乎每日可見，而且大多數(shù)此病患者都具有父代或子代皆有發(fā)病的家族傾向，這就使得針對(duì)此病的研究顯得頗為重要和十分必要。 20世紀(jì)90年代中后期，國(guó)外學(xué)者在軟組織腫瘤的細(xì)胞和分子遺傳學(xué)研究中取得了突破性進(jìn)展，包括針對(duì)脂肪瘤的分子遺傳學(xué)研究，基本證實(shí)脂肪瘤細(xì)胞發(fā)生了染色體易位、重排或融合，這些遺傳學(xué)異常導(dǎo)致了相應(yīng)基因的突變和擴(kuò)增。研究結(jié)果顯示：55~57%的脂肪瘤病例存在染色體異常，主要涉及12q13-15，少數(shù)涉及6p21-23，或丟失13q中的一些成分。位于12q15區(qū)帶上的HMGIC基因（high mobility group IC gen，腫瘤相關(guān)基因高遷移率蛋白IC）重排，現(xiàn)認(rèn)為在脂肪瘤的發(fā)生過程中起了主要作用。研究顯示，t(3:12)(q27-28;q13-15)導(dǎo)致位于12q15上的HMGIC基因與位于3q27-28上的LPP基因融合形成HMGIC-LPP融合基因，斷裂點(diǎn)分別為HMGIC基因?yàn)?號(hào)內(nèi)顯子，LPP基因?yàn)?號(hào)內(nèi)顯子。除t(3;12)(p27-28;q13-15)外，文獻(xiàn)上還報(bào)道了1例t(12;13)(q13-15;q12)，使HMGIC基因與LHFP基因發(fā)生融合。遺憾的是，這些染色體遺傳學(xué)改變后引起哪些相應(yīng)的基因發(fā)生變化，這些變化基因的下游基因表達(dá)如何，其報(bào)道很少。從流行病學(xué)角度來看，目前，比較公認(rèn)的與脂肪瘤發(fā)生、發(fā)展密切相關(guān)的因素主要有如下幾種：1.遺傳因素，臨床中可見父代單發(fā)脂肪瘤，子代出現(xiàn)多發(fā)脂肪瘤或父代多發(fā)，而子代單發(fā)或多發(fā)的情況，這與上述染色體改變學(xué)說剛好能夠互為呼應(yīng)；2.生活習(xí)慣不良，如過度飲酒、高脂飲食、熬夜等；3.生活或工作壓力過大。從文獻(xiàn)檢索來看，近年來，國(guó)內(nèi)外關(guān)于脂肪異常增生性疾病的研究更多傾向于多發(fā)性對(duì)稱性脂肪瘤病以及肥胖的研究，從這些研究中也可以給我們一定的借鑒經(jīng)驗(yàn)，對(duì)于染色體異常所導(dǎo)致的下游基因改變的研究具有相當(dāng)大的參考價(jià)值。通過網(wǎng)絡(luò)信息檢索，，國(guó)內(nèi)也有言論稱脂肪瘤致瘤因子是脂肪瘤形成的真正原因。提出這一理論的人員推測(cè)在脂肪瘤患者體細(xì)胞內(nèi)存在一種致瘤因子，在正常情況下，這種致瘤因子處于一種失活狀態(tài)（無活性狀態(tài)），不會(huì)發(fā)病，但在機(jī)體內(nèi)環(huán)境改變時(shí)，由于體內(nèi)的淋巴細(xì)胞、單核吞噬細(xì)胞等免疫細(xì)胞對(duì)致瘤因子的監(jiān)控能力下降，加之慢性炎癥刺激、全身脂肪代謝異常等誘因條件下，脂肪瘤致瘤因子活性進(jìn)一步增強(qiáng)與細(xì)胞內(nèi)的某些基因片斷結(jié)合，形成基因異常突變，導(dǎo)致脂肪組織沉積，最終形成脂肪瘤（http://www.clsbio.com）。筆者雖經(jīng)多方檢索，但遺憾的是未能找到針對(duì)此項(xiàng)論斷的專業(yè)文獻(xiàn)報(bào)道。但不可否認(rèn)的是，脂肪瘤和其它腫瘤一樣，是正常細(xì)胞通過一系列的基因改變而轉(zhuǎn)變?yōu)槟[瘤細(xì)胞，這種改變可以是遺傳性或后天獲得性，在受到環(huán)境、飲食、輻射和病毒等因素影響引起染色體的變化，從而使mRNA轉(zhuǎn)錄發(fā)生異常，產(chǎn)生過量腫瘤相關(guān)蛋白或結(jié)構(gòu)異常的蛋白，導(dǎo)致細(xì)胞分裂和分化失控，通過多階段、多步驟轉(zhuǎn)變?yōu)槟[瘤細(xì)胞。因此，目前我們已知的是，脂肪瘤的發(fā)病是多因素相互作用的結(jié)果，那么這些因素最終是如何導(dǎo)致脂肪瘤的發(fā)生？在脂肪瘤形成過程中到底是哪些基因發(fā)生了改變？又為什么只是瘤變而多不惡變哪？這些問題的答案還未可知。 針對(duì)上述問題，本課題擬通過基因芯片技術(shù)篩選出脂肪瘤與正常脂肪組織之間存在的相關(guān)差異基因，以期闡釋皮下多發(fā)脂肪瘤的發(fā)病機(jī)制，并為臨床治療提供可能的理論借鑒。 研究目的 本研究旨在通過對(duì)皮下多發(fā)脂肪瘤患者的瘤體與周圍正常脂肪組織的基因差異分析，探索皮下多發(fā)脂肪瘤的相關(guān)基因表達(dá)，為臨床預(yù)防和治療提供可能的理論借鑒。 研究方法 一.樣本采集：來源為長(zhǎng)海醫(yī)院整形外科門診收治的男性皮下多發(fā)脂肪瘤患者，排除全身系統(tǒng)性疾病，平素體健，年齡≤60歲，全身瘤體數(shù)量≥5個(gè)，所有瘤體直徑≤3cm，發(fā)病時(shí)間≤2年，目的是為了便于捕捉脂肪瘤瘤變?cè)缙诘幕虮磉_(dá)差異。同時(shí)采集瘤體周圍正常脂肪組織作為自體對(duì)照樣本，排除個(gè)體差異所造成的基因差異，縮小篩選范圍。 二.實(shí)驗(yàn)分組：1.基因芯片檢測(cè)樣本采集自3個(gè)患者，共6個(gè)，包括脂肪瘤樣本3個(gè)（實(shí)驗(yàn)組，n=3）和脂肪瘤周圍正常脂肪組織樣本3個(gè)（對(duì)照組，n=3）；2.人群散發(fā)皮下多發(fā)脂肪瘤樣本和自體對(duì)照正常脂肪樣本各3個(gè)（n=3）。 三.組織病理學(xué)分析：通過大體觀察、組織病理學(xué)切片HE染色、脂肪組織特殊染色、脂肪瘤內(nèi)血管及神經(jīng)分布，觀察脂肪瘤與正常脂肪組織之間的形態(tài)學(xué)共性和個(gè)性。 四.基因芯片差異基因篩選：應(yīng)用Affymetrix Human U133Plus2.0芯片（人類全基因組芯片）對(duì)實(shí)驗(yàn)組和對(duì)照組共6個(gè)樣本進(jìn)行基因檢測(cè)，所得檢測(cè)結(jié)果通過SBC生物芯片分析系統(tǒng)進(jìn)行差異基因篩選，取差異倍數(shù)（foldchange）2、p0.05的基因?yàn)椴町惢�。�?張基因芯片篩選出的差異基因按照實(shí)驗(yàn)組和對(duì)照組進(jìn)行聚類分析，并根據(jù)分析結(jié)果對(duì)其功能進(jìn)行綜合分析，初步篩選出6個(gè)可能與脂肪瘤發(fā)生、增殖、信號(hào)傳導(dǎo)等功能改變相關(guān)基因作為重要差異基因。 五.相關(guān)基因不同樣本驗(yàn)證：將兩次取材的共6例實(shí)驗(yàn)組樣本及6例對(duì)照組樣本進(jìn)行6個(gè)重要差異基因的RT-PCR驗(yàn)證，排除及證實(shí)基因芯片結(jié)果的可靠性，并綜合基因芯片及RT-PCR兩種檢測(cè)方法所得6個(gè)基因表達(dá)量的差異和分子生物學(xué)功能，初步探討這些基因在脂肪瘤發(fā)生及發(fā)展中可能的作用及機(jī)制。 研究結(jié)果 第一部分皮下多發(fā)脂肪瘤的組織病理學(xué)分析 本課題取材的多發(fā)脂肪瘤均具有完整包膜，包膜細(xì)薄，可見少量血管分布，瘤體色黃，有一定韌性，剖面見脂肪組織質(zhì)地較均一，結(jié)締組織間隔較少，將瘤體分隔為大小不一的小葉。瘤體周圍正常脂肪組織無包膜，被纖維間隔分隔成豆大的小葉狀，單位體積內(nèi)間隔成分較脂肪瘤組織明顯增多。鏡下見脂肪瘤組織內(nèi)主要由分化成熟的脂肪細(xì)胞構(gòu)成，瘤體外周有薄的纖維組織間隔，纖維間隔向內(nèi)伸展，將瘤體分成各個(gè)大小不一的分葉，不同小葉間細(xì)胞大小也具有差異，細(xì)胞擠壓呈圓形或多邊形，細(xì)胞內(nèi)含有大量脂滴脫失后形成的空泡，細(xì)胞核被擠壓偏位呈扁圓或新月狀。間隔內(nèi)有豐富的供血血管和其它類型細(xì)胞成分分布，小葉間排列緊密，小葉內(nèi)的脂肪細(xì)胞大小不一。正常脂肪組織纖維間隔豐富，組織松散，脂肪細(xì)胞形態(tài)大小較脂肪瘤組織更為均一相近，間隔成分主要為纖維結(jié)締組織。特殊染色顯示兩組的細(xì)胞內(nèi)脂滴油紅染色陽(yáng)性。 第二部分皮下多發(fā)脂肪瘤致病相關(guān)基因的基因組學(xué)分析 6例樣本的基因探針結(jié)合總數(shù)為54614個(gè)，脂肪瘤組和正常脂肪組間進(jìn)行統(tǒng)計(jì)學(xué)分析，結(jié)果顯示兩組差異結(jié)合探針總數(shù)共1776個(gè)（p0.05），其中差異倍數(shù)大于兩倍的差異探針結(jié)合數(shù)共374個(gè)。經(jīng)聚類分析，初篩p0.05，F(xiàn)oldchange＞2的差異基因共260個(gè)。與細(xì)胞增殖相關(guān)的結(jié)構(gòu)基因差異數(shù)為36個(gè)，其中上調(diào)基因30個(gè)，下調(diào)基因6個(gè)；2個(gè)凋亡抑制基因ERBB4和NPY5R下調(diào)7倍和4.425倍；具有凋亡雙向調(diào)節(jié)功能的SOX4上調(diào)2.3118倍，具有抗凋亡作用的COMP和HGF分別上調(diào)5.9558和3.366倍，具有凋亡誘導(dǎo)作用的PERP下調(diào)2.387倍；脂類結(jié)合基因10個(gè)，其中上調(diào)基因5個(gè)，下調(diào)基因5個(gè)；脂類儲(chǔ)存正性調(diào)節(jié)基因1個(gè)，即載脂蛋白B基因（APOB）下調(diào)7倍（p=0.0044）；脂類儲(chǔ)存負(fù)向調(diào)節(jié)基因ABCG1上調(diào)2.5倍。另外，與腫瘤細(xì)胞增殖及調(diào)控相關(guān)的幾個(gè)基因ESM1、SOX11及HOXD10等較正常脂肪組的表達(dá)量分別增高32.81倍、31.01倍及13.99倍。結(jié)合各個(gè)基因的生物學(xué)功能和表達(dá)差異，篩選ESM1、SOX11、HOXD10、ERBB4、NPY5R及APOB進(jìn)行散發(fā)人群驗(yàn)證。 第三部分差異基因的散發(fā)人群驗(yàn)證 應(yīng)用RT-PCR驗(yàn)證樣本的脂肪瘤組ESM1、SOX11、HOXD10、ERBB4、NPY5R及APOB的表達(dá)與基因組學(xué)分析結(jié)果基本一致，結(jié)果顯示六個(gè)基因的表達(dá)差異與基因芯片結(jié)果一致，并且每個(gè)樣本的變化特點(diǎn)與基因芯片的信號(hào)強(qiáng)度變化完全符合，應(yīng)用RT-PCR檢測(cè)此六個(gè)基因的差異表達(dá)結(jié)果分別為：ESM1上調(diào)18.51倍，SOX11上調(diào)19.18倍，HOXD10上調(diào)20.55倍，ERBB4下調(diào)16.68倍，NPY5R下調(diào)4.99倍，APOB下調(diào)15.05倍。散發(fā)人群的PCR結(jié)果同樣顯示了與基因芯片相一致的變化規(guī)律，ESM1上調(diào)290.86倍，SOX11上調(diào)6.13倍，HOXD10上調(diào)11.2倍，ERBB4下調(diào)5.09倍， NPY5R下調(diào)7.19倍，APOB下調(diào)15.05倍。既驗(yàn)證了基因芯片結(jié)果的可靠性和穩(wěn)定性，也驗(yàn)證了這六個(gè)差異基因在散發(fā)人群中的表達(dá)差異是確實(shí)存在的。 研究結(jié)論 本課題應(yīng)用基因芯片對(duì)皮下多發(fā)脂肪瘤瘤體與自體正常脂肪之間的差異基因進(jìn)行初步篩選，并從中挑選出兩組差異倍數(shù)較大的致瘤相關(guān)基因3個(gè)（ESM1、SOX11、HOXD10）、細(xì)胞凋亡抑制基因2個(gè)（ERBB4和NPY5R）及脂類儲(chǔ)存調(diào)解基因1個(gè)（APOB），通過熒光定量PCR方法在散發(fā)人群中進(jìn)行驗(yàn)證，初步證實(shí)皮下多發(fā)脂肪瘤的發(fā)生是由于致瘤基因的異常高表達(dá)導(dǎo)致細(xì)胞增殖能力增強(qiáng)，而細(xì)胞死亡和凋亡基因的上調(diào)以及細(xì)胞凋亡抑制基因的低表達(dá)能夠促進(jìn)增殖細(xì)胞的正常凋亡，防止細(xì)胞惡變，另外，脂類儲(chǔ)存和代謝的異常造成脂質(zhì)在胞漿內(nèi)的沉積所造成，初步證實(shí)脂肪瘤的個(gè)體發(fā)生是局部脂肪細(xì)胞增殖造成細(xì)胞數(shù)量增多而非原有脂肪細(xì)胞局部膨大式增長(zhǎng)形成，為揭示脂肪瘤的發(fā)病機(jī)制提供了一定的實(shí)驗(yàn)依據(jù)，并為指導(dǎo)臨床治療提供借鑒。
[Abstract]:Research background
Lipoma (lipoma) is a benign tumor formed by the proliferation of mature adipose tissue. Most textbooks believe that this disease can occur at any age, but most of them are at the age of 40~60. Therefore, the comprehensive study of lipoma has not been paid enough attention to, and the research progress is relatively slow. In clinical work, most doctors will notice that the operation is basically cured and the prognosis is good for the single lipoma, and for the patients with multiple lipoma, the disease will not endanger the life, but it will cause the patient. All day long is worried about the progress of the tumor and the methods and means that can not be completely cured, which seriously affects the physical and mental health and the quality of life of the patients. More importantly, the incidence of subcutaneous lipoma increases with the increasing pressure of the rapid progress of the society, the increase of the bad habits and the change of the diet structure. In the outpatient, the disease is almost daily, and most of the patients have family tendencies of the parent or offspring, which makes it very important and necessary to study the disease.
In the mid and late 1990s, foreign scholars have made breakthroughs in the study of cell and molecular genetics of soft tissue tumors, including the molecular genetics of lipoma, which basically confirmed that the lipoma cells have chromosomal translocation, rearrangement or fusion. These genetic abnormalities lead to the mutation and amplification of the corresponding genes. The results showed that there were chromosomal abnormalities in the cases of 55~57% lipoma, mainly involving 12q13-15, a few involving 6p21-23, or some components in the loss of 13q. The HMGIC gene located in the zone of 12q15 (high mobility group IC gen, tumor related gene high mobility protein IC) rearranged, which is now considered to play a major role in the occurrence of lipoma. The study showed that t (3:12) (3:12) (q27-28; q13-15) resulted in the fusion of HMGIC gene located on 12q15 and the LPP gene located on 3q27-28 to form a HMGIC-LPP fusion gene. The breakpoints were HMGIC gene 3 and LPP gene 8. Besides t (3; 12), 1 cases (12; 13) were reported in the literature. HFP genes are fused. Unfortunately, what corresponding genes are caused by the genetic changes of these chromosomes, and how the downstream genes are expressed in these genes is rarely reported. From an epidemiological point of view, the most commonly recognized factors that are closely related to the occurrence of lipoma are as follows: 1. heredity. Factors, in the clinic, we can see the single lipoma of the father generation, the multiple lipoma of the progeny or the multiple hair of the father generation, and the single or multiple generation of the progeny, which can correspond to the above chromosome change theory. 2. the living habits, such as excessive drinking, high fat diet, stay up late, and so on; 3. life or work pressure too much. Over the years, the research on adipose hyperplastic diseases at home and abroad is more likely to study on multiple symmetric lipomatosis and obesity. From these studies, we can also give us some reference experience and have considerable reference value for the study of the downstream gene changes caused by chromosomal abnormalities. It is also said that lipoma is a real reason for lipoma formation. People who put forward this theory speculate that in the body cells of the lipoma, there is a tumor factor in the body cells of the lipoma. In normal circumstances, the tumor factor is in a inactive state (inactive state) and will not occur, but in the body when the body changes in the body, it is due to the body. The ability of lymphocyte, mononuclear phagocyte and other immune cells to monitor the tumor inducing factor is decreased, in addition to chronic inflammatory stimuli and abnormal body fat metabolism, the activity of the lipoma is further enhanced with some gene fragments in the cell, forming an abnormal mutation, resulting in the formation of adipose tissue and final formation. Lipoma (http://www.clsbio.com). Although the author has been retrieved in many ways, it is regrettable to have failed to find a professional literature report aimed at this argument. But it is undeniable that the lipoma, like other tumors, is a normal cell transformed into a tumor cell through a series of gene changes, which can be inherited or acquired acquired, Factors such as environment, diet, radiation and viruses cause changes in chromosomes, causing abnormal transcription of mRNA, producing excessive tumor related proteins or proteins with abnormal structure, causing cell division and differentiation out of control and transforming into tumor cells through multistage and multistep steps. Therefore, we are now known to be the disease of lipoma. How do these factors ultimately lead to lipoma, and what genes have changed in the course of lipoma? And why does the tumor change and do not change much? The answers to these questions are still unknown.
In order to solve the above problems, we should use gene chip technology to screen out the related differential genes between lipoma and normal adipose tissue, in order to explain the pathogenesis of subcutaneous multiple lipoma and provide possible theoretical reference for clinical treatment.
research objective
The purpose of this study is to explore the gene expression of subcutaneous multiple lipoma by analyzing the gene difference between the tumor body and the normal adipose tissue in the patients with subcutaneous lipoma, and to provide a possible theoretical reference for clinical prevention and treatment.
research method
1. Sample collection: the male subcutaneous multiple lipoma patients were treated in the orthopedics outpatient department of Changhai Hospital, excluding systemic diseases, plain body health, age less than 60 years old, total body number more than 5, all tumor diameter less than 3cm, the onset time was less than 2 years, the aim is to facilitate the capture of the early gene expression difference in lipoma. At the same time, the normal adipose tissue around the tumor was collected as an autologous control sample to exclude the genetic differences caused by individual differences and to narrow the scope of screening.
Two. Experimental group: 1. gene chip detection samples were collected from 3 patients, including 6 samples, including 3 lipoma samples (experimental group, n=3) and 3 normal aliphatic tissue samples (control group, n=3); 2. people distributed subcutaneous lipoma samples and 3 samples of autologous normal fat (n=3).
Three. Histopathological analysis: by gross observation, histopathological section HE staining, special staining of adipose tissue, blood vessels and nerve distribution in lipoma, and observation of morphological generality and personality between lipoma and normal adipose tissue.
Four. Gene chip differential gene screening: Affymetrix Human U133Plus2.0 chip (human genome chip) was used to detect 6 samples of the experimental group and the control group. The results were screened by the SBC biochip analysis system, the difference multiplier (foldchange) 2, and the P0.05 gene were the difference genes. 6 The differential genes selected by Zhang Jiyin chip were cluster analyzed according to the experimental group and the control group. According to the analysis results, the functions were analyzed synthetically, and 6 genes related to lipoma, proliferation and signal transduction were screened out as important differentially genes.
Five. Different samples of related genes were verified: 6 samples of experimental group and 6 cases of control group were tested by RT-PCR to exclude and verify the reliability of gene chip results, and the difference of expression and molecular biological function of 6 bases obtained by integrated gene chip and two detection methods of RT-PCR were synthesized. Objective to explore the possible roles and mechanisms of these genes in the occurrence and development of lipoma.
Research results
The first part is a histopathological analysis of multiple cutaneous lipoma.
The multiple lipoma of this topic have complete capsule, thin film and thin film, a small amount of blood vessel distribution, the tumor is yellow and has a certain toughness. The section shows that the fat tissue is relatively uniform, the connective tissue is less spaced, and the tumor is divided into small and large lobules. The internal septum in the unit volume is more than that of the lipoma. It is found that the lipoma is mainly composed of the mature adipocytes in the lipoma tissue. The tumor is divided into thin fibrous septum in vitro, and the fibrous septum extends inward. The tumor is divided into different lobules of different sizes, and the size of the cells in different lobules is different and the cells are squeezed. The cell contains a large number of circular or polygons. The cell contains a large number of vacuoles formed after the loss of fat drops. The nucleus is compressed and flattened or crescent. There are abundant blood vessels and other types of cell components in the interval. The interlobular arrangement is close, the size of the fat cells in the lobule is different. The normal fat tissue is rich in fiber and loose tissue. The shape and size of adipocytes were more similar than those of lipoma, and the interval components were mainly fibrous connective tissue. Special staining showed that the lipid droplets in the two groups were positive.
The second part is a genomics analysis of the pathogenic genes associated with multiple cutaneous lipoma.
The total number of gene probes in 6 samples was 54614, the lipoma group and the normal fat group were analyzed statistically. The results showed that the total number of differences combined with the total number of probes was 1776 (P0.05), and the difference multiplier was more than two times the number of differential probe binding 374. The difference of the primary screening P0.05 and Foldchange > 2 were 260. The number of structural genes related to cell proliferation was 36, of which 30 were up-regulated and 6 were down regulated; 2 apoptosis suppressor genes, ERBB4 and NPY5R, were down regulated by 7 times and 4.425 times; the SOX4 with bidirectional regulation of apoptosis was 2.3118 times higher than that of COMP and HGF with anti apoptotic effect, and PE with apoptosis inducing effect, respectively. RP was down 2.387 times, and there were 10 lipid binding genes, including 5 up-regulated and 5 down regulated genes, 1 lipid storage positive regulation genes, 7 times down regulation of apolipoprotein B gene (APOB), and 2.5 times up regulation of lipid storage negative regulation gene ABCG1. In addition, several genes related to tumor cell proliferation and regulation, ESM1, SOX11 and HOXD10, etc. The expression of the normal fat group increased 32.81 times, 31.01 times and 13.99 times, respectively. ESM1, SOX11, HOXD10, ERBB4, NPY5R and APOB were screened for sporadic population according to the biological function and expression difference of each gene.
Third parts of the sporadic population of differential genes
The expression of ESM1, SOX11, HOXD10, ERBB4, NPY5R and APOB in the lipoma group with RT-PCR samples was basically consistent with the results of genomic analysis. The results showed that the differences of the expression of six genes were consistent with the gene chip results, and the change characteristics of each sample were in full conformity with the signal intensity changes of the gene chip, and RT-PCR was used to detect this six. The difference expression results were as follows: ESM1 up 18.51 times, SOX11 up 19.18 times up, HOXD10 up 20.55 times, ERBB4 down 16.68 times, NPY5R down 4.99 times, APOB down 15.05 times. PCR results in the sporadic population also showed the same change with gene chip, ESM1 up 290.86 times, SOX11 up 6.13 times up, HOXD10 up 11.2 times up, E RBB4 was down 5.09 times, NPY5R was down 7.19 times, and APOB was down 15.05 times. It not only verified the reliability and stability of the gene chip results, but also proved that the difference in the expression of these six genes in the sporadic population was true.
research conclusion
The gene chip was used to screen the differentially genes between the subcutaneous multiple lipoma tumors and the autologous normal fat, and two groups of two groups, 3 (ESM1, SOX11, HOXD10), and 2 (ERBB4 and NPY5R) and 1 lipid storage mediating genes (APOB), were selected. The quantitative PCR method was validated in sporadic population. It was preliminarily confirmed that the occurrence of multiple cutaneous lipoma was caused by abnormal high expression of tumorigenic gene.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R739.5

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