不同類型肝內(nèi)膽管細胞癌長鏈非編碼RNA差異表達分析及意義
發(fā)布時間:2018-04-23 13:09
本文選題:肝內(nèi)膽管結石 + 肝內(nèi)膽管細胞癌; 參考:《寧波大學》2017年碩士論文
【摘要】:目的:肝內(nèi)膽管細胞癌是一種死亡率較高的惡性腫瘤,其發(fā)病與肝內(nèi)膽管結石密切相關。越來越多的證據(jù)表明,長鏈非編碼RNA參與多種腫瘤的發(fā)生發(fā)展過程。然而它在肝內(nèi)膽管細胞癌(包括結石相關性及非結石相關性肝內(nèi)膽管細胞癌)中的作用目前仍不清楚。因此,本研究旨在探究不同類型肝內(nèi)膽管細胞癌的分子機制差異,并探索結石相關性肝內(nèi)膽管細胞癌相關的長鏈非編碼RNA。方法:通過基因芯片檢測結石相關性及非結石相關性肝內(nèi)膽管癌的lnc RNA及m RNA表達情況,篩選腫瘤相關的差異基因。利用GO基因富集分析和KEGG通路分析進一步分析差異表達的m RNA在兩種類型腫瘤中的功能富集及腫瘤相關信號通路。實時熒光定量PCR用于檢測lnc RNA-AFAP1-AS1在兩種類型肝內(nèi)膽管細胞癌的表達情況并分析其表達水平與臨床病理特征的相關性。此外,通過m RNA-lnc RNA共表達網(wǎng)絡構建及共表達基因功能富集分析預測lnc RNA-AFAP1-AS1功能。結果:基因芯片分析結果顯示兩種不同類型的肝內(nèi)膽管細胞癌的lnc RNA和m RNA的表達模式存在差異。GO富集分析和KEGG通路分析結果亦提示結石相關性肝內(nèi)膽管細胞癌的分子機制不同于非結石相關性肝內(nèi)膽管細胞癌。通過比較篩選出兩類肝內(nèi)膽管細胞癌中表達不同的差異基因,這些可能反映了它們不同的發(fā)病機制。實時熒光定量PCR結果表明,AFAP1-AS1在結石相關性肝內(nèi)膽管細胞癌的腫瘤組織中表達水平高于癌旁組織,而在非結石相關性肝內(nèi)膽管細胞癌中差異無統(tǒng)計學意義。高水平的AFAP1-AS1與腫瘤大小相關。共表達基因富集分析預測其功能主要涉及細胞運動遷移、上皮細胞分化及調節(jié)免疫系統(tǒng)過程。結論:本研究首次描述結石相關性肝內(nèi)膽管細胞癌中l(wèi)nc RNA及m RNA的表達情況,為進一步尋找生物標志物提供有價值的信息。同時證實AFAP1-AS1在結石相關性肝內(nèi)膽管細胞癌中的表達水平上調,其可能在結石致癌過程中發(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.
【學位授予單位】:寧波大學
【學位級別】:碩士
【學位授予年份】:2017
【分類號】:R735.8
【參考文獻】
相關期刊論文 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
,本文編號:1792106
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