本文選題：肝內(nèi)膽管結(jié)石 + 肝內(nèi)膽管細(xì)胞癌��； 參考：《寧波大學(xué)》2017年碩士論文

【摘要】：目的:肝內(nèi)膽管細(xì)胞癌是一種死亡率較高的惡性腫瘤,其發(fā)病與肝內(nèi)膽管結(jié)石密切相關(guān)。越來(lái)越多的證據(jù)表明,長(zhǎng)鏈非編碼RNA參與多種腫瘤的發(fā)生發(fā)展過(guò)程。然而它在肝內(nèi)膽管細(xì)胞癌(包括結(jié)石相關(guān)性及非結(jié)石相關(guān)性肝內(nèi)膽管細(xì)胞癌)中的作用目前仍不清楚。因此,本研究旨在探究不同類(lèi)型肝內(nèi)膽管細(xì)胞癌的分子機(jī)制差異,并探索結(jié)石相關(guān)性肝內(nèi)膽管細(xì)胞癌相關(guān)的長(zhǎng)鏈非編碼RNA。方法:通過(guò)基因芯片檢測(cè)結(jié)石相關(guān)性及非結(jié)石相關(guān)性肝內(nèi)膽管癌的lnc RNA及m RNA表達(dá)情況,篩選腫瘤相關(guān)的差異基因。利用GO基因富集分析和KEGG通路分析進(jìn)一步分析差異表達(dá)的m RNA在兩種類(lèi)型腫瘤中的功能富集及腫瘤相關(guān)信號(hào)通路。實(shí)時(shí)熒光定量PCR用于檢測(cè)lnc RNA-AFAP1-AS1在兩種類(lèi)型肝內(nèi)膽管細(xì)胞癌的表達(dá)情況并分析其表達(dá)水平與臨床病理特征的相關(guān)性。此外,通過(guò)m RNA-lnc RNA共表達(dá)網(wǎng)絡(luò)構(gòu)建及共表達(dá)基因功能富集分析預(yù)測(cè)lnc RNA-AFAP1-AS1功能。結(jié)果:基因芯片分析結(jié)果顯示兩種不同類(lèi)型的肝內(nèi)膽管細(xì)胞癌的lnc RNA和m RNA的表達(dá)模式存在差異。GO富集分析和KEGG通路分析結(jié)果亦提示結(jié)石相關(guān)性肝內(nèi)膽管細(xì)胞癌的分子機(jī)制不同于非結(jié)石相關(guān)性肝內(nèi)膽管細(xì)胞癌。通過(guò)比較篩選出兩類(lèi)肝內(nèi)膽管細(xì)胞癌中表達(dá)不同的差異基因,這些可能反映了它們不同的發(fā)病機(jī)制。實(shí)時(shí)熒光定量PCR結(jié)果表明,AFAP1-AS1在結(jié)石相關(guān)性肝內(nèi)膽管細(xì)胞癌的腫瘤組織中表達(dá)水平高于癌旁組織,而在非結(jié)石相關(guān)性肝內(nèi)膽管細(xì)胞癌中差異無(wú)統(tǒng)計(jì)學(xué)意義。高水平的AFAP1-AS1與腫瘤大小相關(guān)。共表達(dá)基因富集分析預(yù)測(cè)其功能主要涉及細(xì)胞運(yùn)動(dòng)遷移、上皮細(xì)胞分化及調(diào)節(jié)免疫系統(tǒng)過(guò)程。結(jié)論:本研究首次描述結(jié)石相關(guān)性肝內(nèi)膽管細(xì)胞癌中l(wèi)nc RNA及m RNA的表達(dá)情況,為進(jìn)一步尋找生物標(biāo)志物提供有價(jià)值的信息。同時(shí)證實(shí)AFAP1-AS1在結(jié)石相關(guān)性肝內(nèi)膽管細(xì)胞癌中的表達(dá)水平上調(diào),其可能在結(jié)石致癌過(guò)程中發(fā)揮重要作用。
[Abstract]:Objective: intrahepatic cholangiocarcinoma is a malignant tumor with high mortality. There is growing evidence that long-chain non-coding RNA is involved in the development of multiple tumors. However, its role in intrahepatic cholangiocarcinoma (including stone-associated and non-calculous-associated intrahepatic cholangiocarcinoma) remains unclear. Therefore, the purpose of this study was to explore the molecular mechanisms of different types of intrahepatic cholangiocarcinoma and to explore the long chain noncoding RNA associated with lithiasis associated intrahepatic cholangiocarcinoma. Methods: the expression of lnc RNA and m RNA in lithiasis related and non-stone associated intrahepatic cholangiocarcinoma were detected by gene microarray, and the differentially expressed genes were screened. Go gene enrichment analysis and KEGG pathway analysis were used to further analyze the functional enrichment and tumor-related signaling pathway of differentially expressed m RNA in two types of tumors. Real-time fluorescence quantitative PCR was used to detect the expression of lnc RNA-AFAP1-AS1 in two types of intrahepatic cholangiocarcinoma and to analyze the correlation between the expression level and clinicopathological features. In addition, the m RNA-lnc RNA coexpression network was constructed and the function of lnc RNA-AFAP1-AS1 was predicted by functional enrichment analysis of coexpression genes. Results: the results of gene chip analysis showed that the expression patterns of lnc RNA and m RNA in two different types of intrahepatic cholangiocarcinoma were different. Go enrichment analysis and KEGG pathway analysis also suggested that lithiasis associated intrahepatic cholangiocarcinoma. The molecular mechanism is different from that of non-stone-associated intrahepatic cholangiocarcinoma. The differentially expressed genes in two types of intrahepatic cholangiocarcinoma were screened, which may reflect their different pathogenesis. The results of real-time fluorescence quantitative PCR showed that AFAP1-AS1 expression was higher in lithium-associated intrahepatic cholangiocarcinoma than that in paracancerous tissue, but there was no significant difference in non-stone associated intrahepatic cholangiocarcinoma. High levels of AFAP1-AS1 are associated with tumor size. The function of co-expression gene enrichment analysis is mainly related to cell migration, epithelial cell differentiation and regulation of immune system. Conclusion: this study first describes the expression of lnc RNA and m RNA in lithiasis associated intrahepatic cholangiocarcinoma and provides valuable information for further searching for biomarkers. It is also confirmed that the expression of AFAP1-AS1 in lithiasis associated intrahepatic cholangiocarcinoma is up-regulated, which may play an important role in the carcinogenesis of calculi.
【學(xué)位授予單位】：寧波大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R735.8

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相關(guān)期刊論文 前1條

1 Hyo Jung Kim;Jae Seon Kim;Moon Kyung Joo;Beom Jae Lee;Ji Hoon Kim;Jong Eun Yeon;Jong-Jae Park;Kwan Soo Byun;Young-Tae Bak;;Hepatolithiasis and intrahepatic cholangiocarcinoma: A review[J];World Journal of Gastroenterology;2015年48期

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本文編號(hào)：1792106