肝癌生物样本库的标准化建立与信息化管理
DOI: 10.3969/j.issn.1001-5256.2022.05.022
-
摘要:
目的 建立一个小型的拥有标准化操作流程和信息化管理功能的肝癌生物样本库。 方法 根据纳排标准,在患者签署知情同意书基础上,收集2012年8月—2020年12月就诊于华中科技大学同济医学院附属同济医院肝脏外科的肝癌患者血液、组织和粪便样本,并按照全血、血清、冻存组织、石蜡包埋组织和粪便等不同样本的标准流程进行出入库管理,同时采集患者临床信息及其随访信息。通过随机抽取不同年份的肝癌及癌旁冷冻组织样本,检测总RNA的浓度和完整性,确保样本库冷冻样本保存质量。 结果 101个自然月共收集4190例肝癌手术患者样本,其中包括41 718份冷冻组织样本、18 950份石蜡包埋组织样本、24 389份全血样本、20 060份血清样本和5392份粪便样本。所收集肝癌患者的年龄范围是13~88岁,男性占比85.1%,乙型肝炎和肝硬化的比例分别是83.3%和73.5%。根据样本的收集、处理、保存、应用及信息化管理,制定出一份标准的操作流程(SOP)和一套电子数据采集系统(EDC)。从样本库随机抽取的18份冷冻组织样本中,其中16份样本RNA质量较高,可满足后续实验需求。 结论 建立了标准化和信息化的肝癌生物样本库,为肝癌基础研究提供了高质量的样本保障,能挖掘样本更多的研究价值。 Abstract:Objective To establish a small liver cancer biobank with a standard operating procedure and the function of informationized management. Methods According to the inclusion and exclusion criteria, blood, tissue, and stool samples were collected from the patients with liver cancer who attended Liver Surgery Center, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, from August 2012 to December 2020 and signed the informed consent. In-and-out-of-storage management was performed based on the standard procedure for whole blood, serum, frozen tissue, paraffin-embedded tissue, and stool samples, and related clinical and follow-up data were collected. The frozen samples of liver cancer tissue and adjacent tissue in different years were randomly selected, and the concentration and completeness of total RNA were examined to ensure the quality of frozen samples stored in the biobank. Results The samples were collected from 4190 liver cancer patients who underwent surgery within a period of 101 natural months, and there were 41718 frozen tissue samples, 18950 paraffin-embedded tissue samples, 24389 whole blood samples, 20060 serum samples, and 5392 stool samples. The liver cancer patients had an age range of 13-88 years, and male patients accounted for 85.1%. The patients with hepatitis B accounted for 83.3%, and those with liver cirrhosis accounted for 73.5%. A standard operating procedure and an electronic data capture system were developed according to the collection, processing, storage, application, and informationized management of samples. Among the 18 frozen tissue samples randomly selected from the biobank, 16 samples had high RNA quality, which could meet the requirements of subsequent experiments. Conclusion A standardized and informationized biobank has been established for liver cancer, which provides high-quality samples for the basic research on liver cancer and helps to explore the research value of samples. -
Key words:
- Liver Neoplasms /
- Data Collection /
- Biobank
-
表 1 样本库肝癌患者基础信息表
Table 1. The general information of liver cancer patients in biobank
基本信息 例数 年龄(岁) ≤50 1734 >50 2456 性别 男 3566 女 624 饮酒 是 843 否 2796 不详 551 乙型肝炎 是 3492 否 698 肝硬化 是 3081 否 1109 门静脉高压 是 483 否 3062 不详 645 表 2 肝癌组织样本RNA检测结果
Table 2. The RNA detection results on tissue samples of liver cancer
编号 年份 组织部位 浓度(ng/μL) 完整性值 检测结论 1 2012 癌 517 4.30 C 2 2012 癌旁 804 5.60 A 3 2013 癌 557 4.10 C 4 2013 癌旁 501 6.60 A 5 2014 癌 369 5.70 A 6 2014 癌旁 754 6.90 A 7 2015 癌 324 5.80 A 8 2015 癌旁 754 6.90 A 9 2016 癌 509 6.40 A 10 2016 癌旁 500 6.00 A 11 2017 癌 467 5.30 A 12 2017 癌旁 933 9.30 A 13 2018 癌 447 8.20 A 14 2018 癌旁 1148 9.20 A 15 2019 癌 1325 8.60 A 16 2019 癌旁 760 9.50 A 17 2020 癌 945 9.90 A 18 2020 癌旁 477 9.40 A -
[1] Bureau of Medical Administration, National Health Commission of the People's Republic of China. Guidelines for diagnosis and treatment of primary liver cancer in China (2019 edition)[J]. J Clin Hepatol, 2020, 36(2): 277-292. DOI: 10.3969/j.issn.1001-5256.2020.02.007.中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版)[J]. 临床肝胆病杂志, 2020, 36(2): 277-292. DOI: 10.3969/j.issn.1001-5256.2020.02.007. [2] QIU G, JIN Z, CHEN X, et al. Interpretation of guidelines for the diagnosis and treatment of primary liver cancer (2019 edition) in China[J]. Glob Health Med, 2020, 2(5): 306-311. DOI: 10.35772/ghm.2020.01051. [3] CHEN XP. The development of diagnosis and treatment of liver cancer in China[M]. Beijing: People's Medical Publishing House, 2021: 1-19.陈孝平. 中国肝癌诊疗发展历程[M]. 北京: 人民卫生出版社, 2021: 1-19. [4] LI YM, CHEN H, FENG ZD. Surgical treatment of primary liver cancer[J/CD]. Chin J Hepat Surg: Electronic Edition, 2021, 10(4): 343-347. DOI: 10.3877/cma.j.issn.2095-3232.2021.04.001.李玉民, 陈昊, 冯泽东. 原发性肝癌外科治疗[J/CD]. 中华肝脏外科手术学电子杂志, 2021, 10(4): 343-347. DOI: 10.3877/cma.j.issn.2095-3232.2021.04.001. [5] PALMER LJ. UK Biobank: Bank on it[J]. Lancet, 2007, 369(9578): 1980-1982. DOI: 10.1016/S0140-6736(07)60924-6. [6] YUILLE M, van OMMEN GJ, BRÉCHOT C, et al. Biobanking for Europe[J]. Brief Bioinform, 2008, 9(1): 14-24. DOI: 10.1093/bib/bbm050. [7] LI H, NI M, WANG P, et al. A survey of the current situation of clinical biobanks in China[J]. Biopreserv Biobank, 2017, 15(3): 248-252. DOI: 10.1089/bio.2016.0095. [8] LEVY M, CHEN Y, CLARKE R, et al. Socioeconomic differences in health-care use and outcomes for stroke and ischaemic heart disease in China during 2009-16: A prospective cohort study of 0.5 million adults[J]. Lancet Glob Health, 2020, 8(4): e591-e602. DOI: 10.1016/S2214-109X(20)30078-4. [9] ZHOU Y, GE X, SHEN Y, et al. Follow-up of the manganese-exposed workers healthy cohort (MEWHC) and biobank management from 2011 to 2017 in China[J]. BMC Public Health, 2018, 18(1): 944. DOI: 10.1186/s12889-018-5880-0. [10] JACOB F, SALINAS RD, ZHANG DY, et al. A patient-derived glioblastoma organoid model and biobank recapitulates inter-and intra-tumoral Heterogeneity[J]. Cell, 2020, 180(1): 188-204. e22. DOI: 10.1016/j.cell.2019.11.036. [11] CORSO G, GAROSI L, MARRELLI D, et al. Assessment of a tumor bank: A thirty years experience of the University of Siena (Italy)[J]. Cell Tissue Bank, 2015, 16(2): 283-286. DOI: 10.1007/s10561-014-9460-y. [12] CLÉMENT B, CHÊNE G, DEGOS F. A national collection of liver tumours: Lessons learnt from 6 years of biobanking in France[J]. Cancer Lett, 2009, 286(1): 140-144. DOI: 10.1016/j.canlet.2009.04.034. [13] NEUBER AC, TOSTES CH, RIBEIRO AG, et al. The biobank of barretos cancer hospital: 14 years of experience in cancer research[J]. Cell Tissue Bank, 2021. DOI: 10.1007/s10561-021-09941-9. [Online ahead of print]] [14] SONG J, LIU Y, LIU F, et al. The 14-3-3σ protein promotes HCC anoikis resistance by inhibiting EGFR degradation and thereby activating the EGFR-dependent ERK1/2 signaling pathway[J]. Theranostics, 2021, 11(3): 996-1015. DOI: 10.7150/thno.51646. [15] LIAO Z, CHEN L, ZHANG X, et al. PTPRε acts as a metastatic promoter in hepatocellular carcinoma by facilitating recruitment of SMAD3 to TGF-β receptor 1[J]. Hepatology, 2020, 72(3): 997-1012. DOI: 10.1002/hep.31104. [16] HUANG Z, CHU L, LIANG J, et al. H19 promotes HCC bone metastasis through reducing osteoprotegerin expression in a protein phosphatase 1 catalytic subunit alpha/p38 mitogen-activated protein kinase-dependent manner and sponging microRNA 200b-3p[J]. Hepatology, 2021, 74(1): 214-232. DOI: 10.1002/hep.31673. [17] DING ZY, JIN GN, WANG W, et al. Reduced expression of transcriptional intermediary factor 1 gamma promotes metastasis and indicates poor prognosis of hepatocellular carcinoma[J]. Hepatology, 2014, 60(5): 1620-1636. DOI: 10.1002/hep.27273. [18] LIU S, WANG WC, ZHANG H, et al. Best practices for human biobank ethics review in China[J]. Biopreserv Biobank, 2020, 18(4): 274-282. DOI: 10.1089/bio.2019.0132. [19] CAMPBELL LD, ASTRIN JJ, DESOUZA Y, et al. The 2018 revision of the ISBER best practices: Summary of changes and the editorial team's development process[J]. Biopreserv Biobank, 2018, 16(1): 3-6. DOI: 10.1089/bio.2018.0001. [20] International Society for Biological and Environmental repositories (ISBER). 2012 best practices for repositories collection, storage, retrieval, and distribution of biological materials for research international society for biological and environmental repositories[J]. Biopreserv Biobank, 2012, 10(2): 79-161. DOI: 10.1089/bio.2012.1022.