EPS8L3在肝細胞肝癌發(fā)生發(fā)展中的作用及相關(guān)機制研究
發(fā)布時間:2022-01-28 00:24
背景:肝細胞肝癌(hepatocellular carcinoma,HCC)是當(dāng)今世界最為常見的惡性腫瘤之一,其發(fā)病率與死亡率均居所有惡性腫瘤前列。盡管以外科手術(shù)治療為主的綜合治療體系已經(jīng)形成,但目前肝癌治療預(yù)后仍不理想。表皮生長因子受體(epidermal growth factor receptor,EGFR)在惡性腫瘤的發(fā)生發(fā)展過程中起著重要作用。以索拉非尼為代表的EGFR信號通路相關(guān)分子靶向藥物,是目前臨床上使用最為廣泛的抗腫瘤藥物之一;然而,其在肝癌治療中的效果并不十分理想,且耐藥現(xiàn)象逐漸增多,亟需發(fā)現(xiàn)新的有效干預(yù)靶點。表皮生長因子受體通路底物8(epidermal growth factor receptor pathway substrate 8,EPS8)家族的發(fā)現(xiàn),有望為EGFR分子靶向藥物的研發(fā)提供新的靶點選擇,為肝癌的臨床診治提供新的理論依據(jù),具有重要的研究意義與臨床價值。目的:本研究基于公共數(shù)據(jù)庫與臨床樣本,探索EPS8家族成員EPS8L3在肝細胞肝癌中的表達與功能,明確其表達水平與臨床特征間的關(guān)系,通過體內(nèi)外研究闡明其對肝細胞肝癌增殖、遷移與侵襲等能力的影響以...
【文章來源】:浙江大學(xué)浙江省211工程院校985工程院校教育部直屬院校
【文章頁數(shù)】:147 頁
【學(xué)位級別】:博士
【部分圖文】:
-1基于TCGA中肝細胞肝癌數(shù)據(jù)進行表達差異基因篩選的熱圖
-2基于TCGA中肝細胞肝癌數(shù)據(jù)進行表達差異基因篩選的火山圖
經(jīng)R語言分析TCGA肝癌相關(guān)數(shù)據(jù),篩選出EPS8L3基因在肝癌組織中相較于癌旁組織明顯高表達,且其作為表皮生長因子受體通路底物8家族成員,與EGFR具有密切聯(lián)系,目前鮮有文獻予以報道。結(jié)合公共數(shù)據(jù)庫與已報道文獻,簡要繪制EPS8家族成員的蛋白質(zhì)一級結(jié)構(gòu),展示其主要功能結(jié)構(gòu)域以及與EPS8的結(jié)構(gòu)相似性(圖3-2)。3.3結(jié)合TCGA與GTEx數(shù)據(jù)庫分析EPS8家族在肝細胞肝癌中的表達
【參考文獻】:
期刊論文
[1]Mechanisms of hepatocellular carcinoma progression[J]. Olorunseun O Ogunwobi,Trisheena Harricharran,Jeannette Huaman,Anna Galuza,Oluwatoyin Odumuwagun,Yin Tan,Grace X Ma,Minhhuyen T Nguyen. World Journal of Gastroenterology. 2019(19)
[2]2015年中國惡性腫瘤流行情況分析[J]. 鄭榮壽,孫可欣,張思維,曾紅梅,鄒小農(nóng),陳茹,顧秀瑛,魏文強,赫捷. 中華腫瘤雜志. 2019 (01)
[3]Therapeutic targeting of epidermal growth factor receptor in human cancer: successes and limitations[J]. Jill Wykosky,Tim Fenton,Frank Furnari,Webster K. Cavenee. 癌癥. 2011(01)
[4]Antitumor effect of Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, combined with cytotoxic agent on murine hepatocellular carcinoma[J]. Bu-Dong Zhu, Qi-Cheng Zhao, Xin Li, Yan Li, Qi-Ying Lu, Department of Medical Oncology, Peking University School of Oncology and Beijing Institute for Cancer Research, Beijing Cancer Hospital, Beijing 100036, China Shou-Jun Yuan, Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China. World Journal of Gastroenterology. 2005(09)
[5]Effect of epidermal growth factor on cultured rat hepatocytes poisoned by CCl4[J]. 吳斌,王崇文,徐家瑞,祝金泉. Acta Pharmacologica Sinica. 1997(02)
本文編號:3613347
【文章來源】:浙江大學(xué)浙江省211工程院校985工程院校教育部直屬院校
【文章頁數(shù)】:147 頁
【學(xué)位級別】:博士
【部分圖文】:
-1基于TCGA中肝細胞肝癌數(shù)據(jù)進行表達差異基因篩選的熱圖
-2基于TCGA中肝細胞肝癌數(shù)據(jù)進行表達差異基因篩選的火山圖
經(jīng)R語言分析TCGA肝癌相關(guān)數(shù)據(jù),篩選出EPS8L3基因在肝癌組織中相較于癌旁組織明顯高表達,且其作為表皮生長因子受體通路底物8家族成員,與EGFR具有密切聯(lián)系,目前鮮有文獻予以報道。結(jié)合公共數(shù)據(jù)庫與已報道文獻,簡要繪制EPS8家族成員的蛋白質(zhì)一級結(jié)構(gòu),展示其主要功能結(jié)構(gòu)域以及與EPS8的結(jié)構(gòu)相似性(圖3-2)。3.3結(jié)合TCGA與GTEx數(shù)據(jù)庫分析EPS8家族在肝細胞肝癌中的表達
【參考文獻】:
期刊論文
[1]Mechanisms of hepatocellular carcinoma progression[J]. Olorunseun O Ogunwobi,Trisheena Harricharran,Jeannette Huaman,Anna Galuza,Oluwatoyin Odumuwagun,Yin Tan,Grace X Ma,Minhhuyen T Nguyen. World Journal of Gastroenterology. 2019(19)
[2]2015年中國惡性腫瘤流行情況分析[J]. 鄭榮壽,孫可欣,張思維,曾紅梅,鄒小農(nóng),陳茹,顧秀瑛,魏文強,赫捷. 中華腫瘤雜志. 2019 (01)
[3]Therapeutic targeting of epidermal growth factor receptor in human cancer: successes and limitations[J]. Jill Wykosky,Tim Fenton,Frank Furnari,Webster K. Cavenee. 癌癥. 2011(01)
[4]Antitumor effect of Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, combined with cytotoxic agent on murine hepatocellular carcinoma[J]. Bu-Dong Zhu, Qi-Cheng Zhao, Xin Li, Yan Li, Qi-Ying Lu, Department of Medical Oncology, Peking University School of Oncology and Beijing Institute for Cancer Research, Beijing Cancer Hospital, Beijing 100036, China Shou-Jun Yuan, Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China. World Journal of Gastroenterology. 2005(09)
[5]Effect of epidermal growth factor on cultured rat hepatocytes poisoned by CCl4[J]. 吳斌,王崇文,徐家瑞,祝金泉. Acta Pharmacologica Sinica. 1997(02)
本文編號:3613347
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