本文選題：皮膚鱗狀細(xì)胞癌 + RRBS�。� 參考：《北京協(xié)和醫(yī)學(xué)院》2017年碩士論文

【摘要】：背景皮膚鱗狀細(xì)胞癌是一種起源于表皮及其附屬器角質(zhì)形成細(xì)胞的惡性腫瘤。皮膚鱗狀細(xì)胞癌發(fā)病率在皮膚惡性腫瘤中僅次于皮膚基底細(xì)胞癌,占第二位,該病的發(fā)病率較高,且處于不斷上升之中。由于皮膚鱗狀細(xì)胞癌的發(fā)病率日益增高,有較高的局部及遠(yuǎn)處轉(zhuǎn)移率,因此對(duì)其發(fā)病機(jī)理的研究日漸引起人們的重視。表觀遺傳學(xué)即在不改變基因組序列的前提下,通過DNA甲基化和組蛋白修飾來調(diào)控基因表達(dá)。DNA甲基化狀態(tài)的改變是引起腫瘤的一個(gè)重要因素,這種變化包括基因組整體甲基化水平降低和CpG島局部甲基化水平的異常升高,從而導(dǎo)致基因組的不穩(wěn)定和抑癌基因的不表達(dá)。目的篩選出候選基因,并初步驗(yàn)證其在皮膚鱗狀細(xì)胞癌發(fā)病中的表觀遺傳學(xué)作用。方法采用RRBS方法檢測(cè)皮膚鱗狀細(xì)胞癌及癌旁組織基因組甲基化水平,采用RNA-Seq方法檢測(cè)皮膚鱗狀細(xì)胞癌及癌旁組織基因轉(zhuǎn)錄組,篩選出皮膚鱗狀細(xì)胞癌異常甲基化基因,擴(kuò)大樣本量,采用QPCR方法進(jìn)行目的基因mRNA水平的檢測(cè)。結(jié)果通過RRBS和RNA-seq技術(shù),本研究共獲得了 ACACB等23個(gè)候選基因。擴(kuò)大樣本驗(yàn)證,結(jié)果顯示,皮膚鱗狀細(xì)胞癌中這些目的基因mRNA水平降低。結(jié)論目的基因啟動(dòng)子區(qū)域的異常甲基化可能參與了皮膚鱗狀細(xì)胞癌的發(fā)病過程,需要進(jìn)一步研究其在該病中的表觀遺傳功能。
[Abstract]:Background skin squamous cell carcinoma (SCC) is a malignant tumor originating from keratinocytes of epidermis and its appendages.The incidence of cutaneous squamous cell carcinoma (SCC) is second only to cutaneous basal cell carcinoma (BCC).Since the incidence of cutaneous squamous cell carcinoma (SCC) is increasing and the rate of local and distant metastasis is high, the study on the pathogenesis of SCC has attracted more and more attention.Epigenetics, which regulates gene expression and methylation through DNA methylation and histone modification without changing genomic sequence, is an important factor that causes tumor.These changes include a decrease in the global methylation level of the genome and an abnormal increase in the local methylation level of the CpG island, leading to genomic instability and non-expression of tumor suppressor genes.Objective to screen candidate genes and preliminarily verify their epigenetic role in the pathogenesis of cutaneous squamous cell carcinoma (SCC).Methods the genomic methylation level of skin squamous cell carcinoma and adjacent tissues was detected by RRBS method, and the abnormal methylation gene of skin squamous cell carcinoma was screened by RNA-Seq assay.The mRNA level of target gene was detected by QPCR method.Results A total of 23 candidate genes such as ACACB were obtained by RRBS and RNA-seq techniques.The results of expanded sample validation showed that mRNA levels of these target genes decreased in cutaneous squamous cell carcinoma.Conclusion the abnormal methylation of gene promoter region may be involved in the pathogenesis of cutaneous squamous cell carcinoma, and its epigenetic function should be further studied.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【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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