肝癌具有高度侵袭性和复发率,是我国常见恶性肿瘤之一。由于肝癌早期症状很不明显,早期诊断又比较困难,因此具有很高的致死率。早期诊断是预防肝癌、提高肝癌患者生存率最重要的措施之一,筛选和鉴定肝癌的早期诊断标志物是首要任务,利于相关组学研究技术来探寻新的诊疗方法刻不容缓,通过寻找新的特异性肝癌分子标志物,以建立更全面更有效的分子分型分层系统,通过早期诊断提高肝癌患者的生存率。本文对传统的、潜在的肝癌早期诊断标志物及其检测方法的研究进展作一综述。
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China with high invasive and recurrence rate. Because the early symptoms of liver cancer are not obvious and the early diagnosis is difficult, it has a high mortality rate. Early diagnosis is one of the most important measures to prevent liver cancer and improve the survival rate of patients with liver cancer. Screening and early diagnosis markers for the identification of cancer of the liver are the primary task. It is urgent to explore new methods of diagnosis and treatment with the help of related omics research techniques, by finding new specific molecular markers of liver cancer, to establish a more comprehensive and more effective molecular classification layered system, and improve survival of patients with liver cancer by early diagnosis. This paper reviews the research progress of traditional and potential markers for early diagnosis of liver cancer and their detection methods.
肝癌,早期诊断,分子标志物,组学,检测方法, Liver Cancer Early Diagnosis Molecular Markers Omics Detection Methods肝癌分子诊断标志物及相关组学技术 研究进展
汤忠琼,肖 瑶,王 峰. 肝癌分子诊断标志物及相关组学技术研究进展Advances in Molecular Diagnostic Markers and Related Omics Techniques for Liver Cancer[J]. 临床医学进展, 2019, 09(01): 61-66. https://doi.org/10.12677/ACM.2019.91012
参考文献ReferencesVineis, P. and Wild, C.P. (2014) Global Cancer Patterns: Causes and Prevention. Lancet, 383, 549-557.
<br>https://doi.org/10.1016/S0140-6736(13)62224-2王丹霞, 全文婕, 史晓欣, 等. 肝癌早期诊断标志物及其检测方法的研究进展[J]. 肿瘤药学, 2016, 6(1): 15-20.Yu, L.X. and Schwabe, R.F. (2017) The Gut Microbiome and liver Cancer: Mechanisms and Clinical Translation. Nature Reviews Gastroenterology & Hepatology, 14, 527-539. <br>https://doi.org/10.1038/nrgastro.2017.72Ren, Z., et al. (2018) Gut Microbiome Analysis as a Tool towards Targeted Non-Invasive Biomarkers for Early Hepatocellular Carcinoma. Gut, gutjnl-2017-315084.周进学. 基于肿瘤基因高通量捕获测序技术的肝癌分子分型研究[D]: [博士学位论文]. 郑州: 郑州大学, 2016.Wooden, B., et al. (2017) Using Big Data to Discover Diagnostics and Therapeutics for Gastrointestinal and Liver Diseases. Gastroenterology, 152, 53-67. <br>https://doi.org/10.1053/j.gastro.2016.09.065Breuhahn, K., Gores, G. and Schirmacher, P. (2011) Strategies for Hepatocellular Carcinoma Therapy and Diagnostics: Lessons Learned from High Throughput and Profiling Approaches. Hepatology, 53, 2112-2121.
<br>https://doi.org/10.1002/hep.24313邵雪. 基于HPLC/TripleTOF-MS/MS技术慢性乙型肝炎感染不同阶段的代谢组学研究[D]: [博士学位论文]. 长春: 吉林大学, 2012.Takashima, M., et al. (2006) Proteomic Analysis of Autoantibodies in Patients with Hepatocellular Carcinoma. Proteomics, 6, 3894-3900. <br>https://doi.org/10.1002/pmic.200500346李克, 曹璐颖. 血清蛋白质组学技术在肿瘤血清标志物筛选中的应用[J]. 医学研究杂志, 2012, 41(9): 18-21.Mustafa, M.Z., et al. (2016) Autoantibody Signatures Defined by Serological Proteome Analysis in Sera from Patients with Cholangiocarcinoma. Journal of Translational Medicine, 14, 17. <br>https://doi.org/10.1186/s12967-015-0751-2同颖娜, 李丹. microRNA的液体芯片检测方法[J]. 分子诊断与治疗杂志, 2011, 3(3): 200-202.梁惠仪, 彭娟, 李明, 等. 液体芯片技术定量测定人体血清CEA、AFP、NSE和tPSA [J]. 分子诊断与治疗杂志, 2010, 2(4): 266-271.Chen, L., et al. (2010) Enhanced Detection of Early Hepatocellular Carcinoma by Serum SELDI-TOF Proteomic Signature Combined with Alpha-Fetoprotein Marker. Annals of Surgical Oncology, 17, 2518-2525.
<br>https://doi.org/10.1245/s10434-010-1038-8Lu, H.B., et al. (2010) Five Serum Proteins Identified Using SELDI-TOF-MS as Potential Biomarkers of Gastric Cancer. Japanese Journal of Clinical Oncology, 40, 336-342. <br>https://doi.org/10.1093/jjco/hyp175Della, C.C., et al. (2016) Early Diagnosis of Liver Cancer: An Appraisal of International Recommendations and Future Perspectives. Liver International, 36, 166-176. <br>https://doi.org/10.1111/liv.12965Huang, T.S., et al. (2013) Diagnostic Performance of Alpha-Fetoprotein, Lens Culinaris Agglutinin-Reactive Alpha-Fetoprotein, Des-Gamma Carboxyprothrombin, and Glypican-3 for the De-tection of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis Protocol. Systematic Reviews, 2, 37. <br>https://doi.org/10.1186/2046-4053-2-37梁广舒, 顾志冬. 脱-γ-羧基凝血酶原的基础和临床研究进展[J]. 诊断学理论与实践, 2016(5): 532-536.Jiang, K., et al. (2016) Aberrant Expression of Golgi Protein 73 Is Indic-ative of a Poor Outcome in Hepatocellular Carcinoma. Oncology Reports, 35, 2141-2150. <br>https://doi.org/10.3892/or.2016.4601Maitra, A. and Thuluvath, P.J. (2004) GP73 and Liver Disease: A (Golgi) Complex Enigma. The American Journal of Gastroenterology, 99, 1096-1098. <br>https://doi.org/10.1111/j.1572-0241.2004.40410.xNing, S., et al. (2012) Glypican-3, a Novel Prognostic Marker of Hepatocellular Cancer, Is Related with Postoperative Metastasis and Recurrence in Hepatocellular Cancer Patients. Molecular Biology Reports, 39, 351-357.
<br>https://doi.org/10.1007/s11033-011-0745-yKandil, D., et al. (2007) Glypican-3 Immunocytochemistry in Liver Fine-Needle Aspirates: A Novel Stain to Assist in the Differentiation of Benign and Malignant Liver Lesions. Cancer, 111, 316-322. <br>https://doi.org/10.1002/cncr.22954Pogribny, I.P. (2018) MicroRNAs as Biomarkers for Clinical Studies. Experimental Biology and Medicine (Maywood), 243, 283-290. <br>https://doi.org/10.1177/1535370217731291Wen, Y., et al. (2015) Plasma miRNAs as Early Biomarkers for Detecting Hepatocellular Carcinoma. International Journal of Cancer, 137, 1679-1690. <br>https://doi.org/10.1002/ijc.29544Vogtmann, E. and Goedert, J.J. (2016) Epidemiologic Studies of the Human Microbiome and Cancer. British Journal of Cancer, 114, 237-242. <br>https://doi.org/10.1038/bjc.2015.465Wan, M. and El-Nezami, H. (2018) Targeting Gut Microbiota in Hepatocellular Carcinoma: Probiotics as a Novel Therapy. Hepatobiliary Surgery and Nutrition, 7, 11-20. <br>https://doi.org/10.21037/hbsn.2017.12.07刘珍, 邓天好, 尹抗抗, 等. 肝复方对原发性肝癌模型小鼠肠道菌群影响的实验研究[J]. 湖南中医杂志, 2017, 33(7): 167-169.Qin, N., et al. (2014) Alterations of the Human Gut Microbiome in Liver Cirrhosis. Nature, 513, 59-64.
<br>https://doi.org/10.1038/nature13568Tozun, N. and Vardareli, E. (2016) Gut Microbiome and Gastrointestinal Cancer. Journal of Clinical Gastroenterology, 50, S191-S196. <br>https://doi.org/10.1097/MCG.0000000000000714李可欣, 马浩然, 张男男, 等. 肠道菌群在肝癌中的作用研究进展[J]. 实用医学杂志, 2018(9): 1575-1578.Rozeik, M.S., et al. (2017) Evaluation of CD44 and CD133 as Markers of Liver Cancer Stem Cells in Egyptian Patients with HCV-Induced Chronic Liver Diseases versus Hepatocellular Carcinoma. Electron Physician, 9, 4708-4717.
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