本文選題：胃固有肌層間質(zhì)瘤 + 基因芯片　； 參考：《青島大學(xué)》2017年碩士論文

【摘要】：目的:利用基因芯片技術(shù)對起源于胃固有肌層間質(zhì)瘤及瘤周組織標(biāo)本基因表達(dá)譜進(jìn)行對比分析,篩選出胃間質(zhì)瘤發(fā)生和發(fā)展過程中異常表達(dá)的基因,尋找顯著差異基因,初步探討胃固有肌層間質(zhì)瘤及其瘤周組織基因表達(dá)的變化特征及其可能存在的生物信息學(xué)意義,以期指導(dǎo)胃間質(zhì)瘤精準(zhǔn)診斷及藥物靶向治療。方法:選取青島大學(xué)附屬煙臺毓璜頂醫(yī)院經(jīng)內(nèi)鏡及腹腔鏡治療、病理檢查及免疫組化檢測證實(shí)為胃間質(zhì)瘤患者各3例。術(shù)前均行小探頭超聲胃鏡檢查提示病灶起源于胃固有肌層,術(shù)中收集胃固有肌層間質(zhì)瘤組織及與其配對的瘤周組織標(biāo)本,每例標(biāo)本于離體后即刻置于液氮中冰凍保存以備用。分別抽提胃固有肌層組織及瘤周正常組織總RNA,反轉(zhuǎn)錄合成cDNA,經(jīng)體外轉(zhuǎn)錄(IVT)同時(shí)摻入biotin生物素標(biāo)記合成cRNA探針,然后進(jìn)行cRNA純化及片段化,將片段化后的cRNA配制成適宜雜交的反應(yīng)體系,并與Affymetrix mRNA表達(dá)譜芯片進(jìn)行雜交。按照差異倍數(shù)法標(biāo)準(zhǔn)篩選出差異基因;而對這些差異基因進(jìn)行基因功能注釋、富集及通路分析,則采用PANTHER/KEGG數(shù)據(jù)庫及Gene Ontology(GO)功能分析軟件實(shí)現(xiàn),篩選出與腫瘤發(fā)生發(fā)展相關(guān)的基因功能類和涉及的信號通路。結(jié)果:1.按照差異顯著性標(biāo)準(zhǔn),與瘤周正常組織比較,發(fā)現(xiàn)胃固有肌層間質(zhì)瘤組織中共找到3293條差異表達(dá)基因,其中上調(diào)基因有2588個,下調(diào)基因有705個,尤以DPP10、ETV1、DKK4、CXCL14、MT1M等基因差異表達(dá)最為明顯。2.這些差異表達(dá)基因功能大致分為細(xì)胞分化、細(xì)胞增殖調(diào)節(jié)、細(xì)胞粘附、細(xì)胞信號轉(zhuǎn)導(dǎo)、細(xì)胞骨架結(jié)構(gòu)等等多種生物學(xué)過程,并涉及多條與腫瘤相關(guān)信號傳導(dǎo)通路,如Wnt信號通路、Ras信號通路、Rap1信號通路、P13K-AKT信號通路、細(xì)胞外基質(zhì)受體相互作用等。結(jié)論:胃固有肌層間質(zhì)瘤組織與瘤周組織之間存在諸如DPP10、ETV1、DKK4、CXCL14、MT1M等多條明顯差異性表達(dá)基因,這些差異表達(dá)基因可能調(diào)控著胃間質(zhì)瘤的發(fā)生和發(fā)展,為尋找胃固有肌層間質(zhì)瘤新的分子標(biāo)記物或治療新靶點(diǎn)提供了重要的生物學(xué)依據(jù)及參考。若能進(jìn)一步深入探究這些差異表達(dá)基因及其所涉及的相關(guān)的調(diào)控通路,將對有效的及早診治胃間質(zhì)瘤、提高胃間質(zhì)瘤患者長期生存率和生存質(zhì)量具有重要的臨床指導(dǎo)意義。
[Abstract]:Objective: to compare and analyze the gene expression profiles of specimens derived from gastric propria muscular stromal tumors (GIST) and surrounding tissues by using gene chip technique, and to screen out the abnormal expression genes during the occurrence and development of gastric stromal tumors (GIST), and to search for significant difference genes. To explore the characteristics of gene expression and its possible bioinformatics significance in gastric propria muscular stromal tumors and its surrounding tissues in order to guide the accurate diagnosis and drug targeted therapy of gastric stromal tumors. Methods: three cases of gastric stromal tumors were confirmed by endoscopy and laparoscopy in Yantai Yuzhouding Hospital affiliated to Qingdao University. Before operation, small probe gastroscopy showed that the lesion originated from the lamina propria muscularis of the stomach. During the operation, specimens of stromal tissue of gastric propria myometrium were collected and matched with them. Each specimen was frozen and stored in liquid nitrogen immediately after the operation. Total RNAs were extracted from the muscularis propria of stomach and normal tissues around the tumor respectively, and cDNAs were synthesized by reverse transcription. CRNA probes were synthesized by incorporation of biotin labeled by in vitro transcription, and then cRNA was purified and segmented. The segmented cRNA was prepared into a suitable hybridization reaction system and hybridized with Affymetrix mRNA expression microarray. The differentially expressed genes were screened according to the standard of differential multiple method, and the function analysis software of PANTHER/KEGG database and Gene Ontology goo was used to analyze the function of these differentially expressed genes. Gene functional classes and signaling pathways involved in tumorigenesis and progression were screened. The result is 1: 1. According to the standard of significant difference, 3293 differentially expressed genes were found in gastric propria muscular stromal tumors, including 2588 up-regulated genes and 705 down-regulated genes. The differential expression of DPP10, ETV1, DKK4, CXCL14, MT1M and other genes was the most obvious. The function of these differentially expressed genes can be divided into many biological processes, such as cell differentiation, regulation of cell proliferation, cell adhesion, cell signal transduction, cytoskeleton structure, and many signal transduction pathways related to tumor. For example Wnt signaling pathway Ras signaling pathway Rap1 signal pathway P13K-AKT signal pathway extracellular matrix receptor interaction and so on. Conclusion: there are many distinct differentially expressed genes, such as DPP10, ETV1, DKK4, CXCL14, MT1M, between the tissues of gastric intrinsic muscular stromal tumors and surrounding tissues. These differentially expressed genes may regulate the occurrence and development of gastric stromal tumors. It provides important biological basis and reference for finding new molecular markers or new targets for treatment of gastric propria muscular stromal tumors. If we can further explore these differentially expressed genes and their related regulatory pathways, it will be of great clinical significance for the diagnosis and treatment of gastric stromal tumors as soon as possible, and for improving the long-term survival rate and quality of life of patients with gastric stromal tumors.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735.2

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