中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

术前外周血单个核细胞微RNA-192对孤立性肝细胞癌微血管侵犯的预测价值

丁雪梅 武世伦 孙文兵

引用本文:
Citation:

术前外周血单个核细胞微RNA-192对孤立性肝细胞癌微血管侵犯的预测价值

DOI: 10.3969/j.issn.1001-5256.2021.05.028
基金项目: 

国家自然科学基金 (81572957)

利益冲突声明:本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明:丁雪梅负责课题设计,资料分析,撰写论文;武世伦负责收集数据,修改论文;孙文兵负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    作者简介:

    丁雪梅(1971—),女,博士,副主任医师,主要从事肝胆胰脾外科研究

    通信作者:

    孙文兵,sunwb_1121@126.com

  • 中图分类号: R735.7

Value of preoperative microRNA-192 in peripheral blood mononuclear cells in predicting microvascular invasion of solitary hepatocellular carcinoma

  • 摘要:   目的  探讨术前外周血单个核细胞微RNA(miRNA, miR)-192对孤立性肝细胞癌(简称肝癌)血管侵犯(MVI)的预测价值。  方法  选取2018年3月—2020年4月于北京朝阳医院西区肝胆胰脾外科接受手术治疗的HCC患者136例,收集患者相关资料,术前行超声检查,并检测患者外周血单个核细胞miR-192表达情况。根据术后病理检查是否有MVI分为MVI组(n=41)和非MVI组(n=95)。计量资料2组间比较采用t检验,计数资料2组间比较采用χ2检验。对可能影响MVI的各因素进行单因素及多因素logistic回归分析,采用ROC曲线分析术前miR-192表达对MVI的预测价值。  结果  MVI组患者术前外周血单个核细胞miR-192相对表达量明显低于非MVI组,差异有统计学意义(0.798±0.164 vs 1.086±0.215,t=7.663, P<0.01)。多因素logistic回归分析结果显示,术前miR-192(OR=3.999,95%CI: 1.585~10.086,P=0.003)、结节类型(OR=3.241,95%CI: 1.154~9.106,P=0.026)以及包膜类型(OR=2.776,95%CI: 1.088~7.084,P=0.033)是影响肝癌患者MVI发生的独立危险因素。术前外周血单个核细胞miR-192预测MVI的ROC曲线下面积为0.872,,95%CI: 0.768~0.931,敏感度68.38%、特异度70.59%,最佳截断值为0.858。  结论  术前外周血单个核细胞miR-192与孤立性肝癌患者MVI的发生有密切联系,术前miR-192偏低、多结节以及无包膜将增加MVI的发生风险,术前miR-192水平对孤立性肝癌MVI具有良好的预测价值。

     

  • 图  1  术前外周血单个核细胞miR-192预测MVI的ROC曲线结果

    表  1  引物序列

    引物 序列
    miR-192 上游引物:5′-CTGACCTATGAATTGACAGCC-3′
    下游引物:5′-TTAGGCTCCAGACGGTTTAT-3′
    U6 上游引物:5′-CTCGCTTCGGCAGCACA-3′
    下游引物:5′-TCTGCGACTATAAATACGA-3′
    下载: 导出CSV

    表  2  MVI发生单因素分析

    因素 MVI组(n=41) 非MVI组(n=95) 统计值 P
    性别(例) χ2=0.138 0.710
      男 23 50
      女 18 45
    年龄(岁) 50.72±9.17 49.87±10.22 t=0.459 0.647
    肿瘤直径(cm) 5.64±2.16 4.28±1.78 t=3.828 <0.001
    肿瘤位置(例) χ2=1.434 0.152
      跨叶 9 12
      左叶 15 33
      右叶 17 50
    结节类型(例) χ2=5.422 <0.001
      类圆型 15 78
      单结节型 14 13
      多结节型 12 4
    包膜类型(例) χ2=5.914 <0.001
      包膜完整 9 69
      包膜缺损 14 19
      无包膜 18 7
    Child-Pugh分级(例) χ2=0.416 0.519
      A级 27 57
      B级 14 38
    肝硬化(例) χ2=0.558 0.455
      有 24 49
      无 17 46
    下载: 导出CSV

    表  3  多因素logistic回归分析

    因素 B SE Wald P OR 95%CI
    术前miR-192(偏低vs偏高) 1.386 0.472 8.623 0.003 3.999 1.585~10.086
    结节类型(多结节vs单结节) 1.176 0.527 4.980 0.026 3.241 1.154~9.106
    包膜类型(无包膜vs有包膜) 1.021 0.478 4.562 0.033 2.776 1.088~7.084
    下载: 导出CSV
  • [1] KULIK L, EI-SERAG HB. Epidemiology and management of hepatocellular carcinoma[J]. Gastroenterology, 2019, 156(2): 477-491. e1. http://www.sciencedirect.com/science/article/pii/S0891552010000590
    [2] WILSON GC, GELLER DA. Evolving surgical options for hepatocellular carcinoma[J]. Surg Oncol Clin N Am, 2019, 28(4): 645-661. DOI: 10.1016/j.soc.2019.06.006.
    [3] GAO H, WEN SJ, ZHANG X, et al. Preoperative risk factor analysis and prediction model establishment of microvascular invasion in small hepatocellular carcinoma[J]. Chin J Gen Surg, 2019, 34(11): 921-924. DOI: 10.3670.cma.j.issn.1007-631X.2019.11.003.

    高航, 翁山耕, 张翔, 等. 小肝癌合并微血管侵犯的术前危险因素分析及预测模型构建[J]. 中华普通外科杂志, 2019, 34(11): 921-924. DOI: 10.3670.cma.j.issn.1007-631X.2019.11.003.
    [4] TIWARI A, MUKHERJEE B, DIXIT M. MicroRNA key to angiogenesis regulation: MiRNA biology and therapy[J]. Curr Cancer Drug Targets, 2018, 18(3): 266-277. DOI: 10.2174/1568009617666170630142725.
    [5] LIU C, SONG Z. Relationship between microRNA-21 and TLRs/NF-κB signaling pathway in peripheral blood mononuclear cells of rats with hepatocellular carcinoma[J]. Chin Hepatol, 2018, 23(2): 162-164. DOI: 10.3969/j.issn.1008-1704.2018.02.020.

    刘驰, 宋展. 肝癌大鼠癌组织microRNA-21与外周血单个核细胞TLRs/NF-κB信号通路的关系[J]. 肝脏, 2018, 23(2): 162-164. DOI: 10.3969/j.issn.1008-1704.2018.02.020.
    [6] Liver cancer committee of China Anti Cancer Association, Hepatology group of Hepatology branch of Chinese Medical Association, Pathology Committee of China Anti Cancer Association, et al. Evidence-based practice guidelines for the standardized pathological diagnosis of primary liver cancer in China (2015 update)[J]. J Clin Hepatol, 2015, 31(6): 833-839. DOI: 10.3969/j.issn.1001-5256.2015.06.004.

    中国抗癌协会肝癌专业委员会, 中华医学会肝病学分会肝癌学组, 中国抗癌协会病理专业委员会, 等. 原发性肝癌规范化病理诊断指南(2015年版)[J]. 临床肝胆病杂志, 2015, 31(6): 833-839. DOI: 10.3969/j.issn.1001-5256.2015.06.004.
    [7] ZENG F, CHEN B, ZENG J, et al. Preoperative neutrophil-lymphocyte ratio predicts the risk of microvascular invasion in hepatocellular carcinoma: A meta-analysis[J]. Int J Biol Markers, 2019, 34(3): 213-220. DOI: 10.1177/1724600819874487.
    [8] NITTA H, ALLARD MA, SEBAGH M, et al. Predictive model for microvascular invasion of hepatocellular carcinoma among candidates for either hepatic resection or liver transplantation[J]. Surgery, 2019, 165(6): 1168-1175. DOI: 10.1016/j.surg.2019.01.012.
    [9] YANG GH, GAO ZL, SUN WJ, et al. The risk factors of microvascular invasion in hepatocellular carcinoma based on CT characteristics[J]. J Pract Radiol, 2020, 36(8): 1248-1252, 1265. DOI: 10.3969/j.issn.1002-1671.2020.08.018.

    杨冠华, 高知玲, 孙文杰, 等. 基于CT特征肝细胞癌微血管侵犯危险因素研究[J]. 实用放射学杂志, 2020, 36(8): 1248-1252, 1265. DOI: 10.3969/j.issn.1002-1671.2020.08.018.
    [10] BAI X, MA ZH, HAO ZQ, et al. Research advances in the risk factors for microvascular invasion in hepatocellular carcinoma[J]. J Clin Hepatol, 2019, 35(11): 2578-2581. DOI: 10.3969/j.issn.1001-5256.2019.11.042.

    白雪, 马作红, 郝志强, 等. 肝细胞癌微血管侵犯相关危险因素[J]. 临床肝胆病杂志, 2019, 35(11): 2578-2581. DOI: 10.3969/j.issn.1001-5256.2019.11.042.
    [11] ERSTAD DJ, TANABE KK. Prognostic and therapeutic implications of microvascular invasion in hepatocellular carcinoma[J]. Ann Surg Oncol, 2019, 26(5): 1474-1493. DOI: 10.1245/s10434-019-07227-9.
    [12] SOTIROPOULOS GC, MACHAIRAS N, FOUZAS I, et al. Prediction of microvascular tumor invasion in liver transplant candidates with hepatocellular carcinoma: A feasible concept or a misleading illusion?[J]. Transplant Proc, 2019, 51(2): 421-423. DOI: 10.1016/j.transproceed.2019.01.016.
    [13] AST V, KORDAβ T, OSWALD M, et al. MiR-192, miR-200c and miR-17 are fibroblast-mediated inhibitors of colorectal cancer invasion[J]. Oncotarget, 2018, 9(85): 35559-35580. DOI: 10.18632/oncotarget.26263.
    [14] ZOU P, ZHU M, LIAN C, et al. miR-192-5p suppresses the progression of lung cancer bone metastasis by targeting TRIM44[J]. Sci Rep, 2019, 9(1): 19619. DOI: 10.1038/s41598-019-56018-5.
    [15] ZHAO J, XU J, ZHANG R. SRPX2 regulates colon cancer cell metabolism by miR-192/215 via PI3K-Akt[J]. Am J Transl Res, 2018, 10(2): 483-490. http://europepmc.org/abstract/MED/29511442
    [16] GU Y, WEI X, SUN Y, et al. miR-192-5p silencing by genetic aberrations is a key event in hepatocellular carcinomas with cancer stem cell features[J]. Cancer Res, 2019, 79(5): 941-953. DOI: 10.1158/0008-5472.CAN-18-1675.
    [17] LI Y, ZHANG J, YAN LM. Values of miR-9, miR-192 and miR-205 in diagnosis of cervical cancer[J]. J Nanchang Univ(Med Sci Edition), 2020, 60(3): 74-77, 97. DOI: 10.13764/j.cnki.ncdm.2020.03.016.

    李艳, 张锦, 闫丽明. miR-9、miR-192和miR-205在宫颈癌诊断中的价值[J]. 南昌大学学报(医学版), 2020, 60(3): 74-77, 97. DOI: 10.13764/j.cnki.ncdm.2020.03.016.
    [18] DU X, QI F, LU S, et al. Nicotine upregulates FGFR3 and RB1 expression and promotes non-small cell lung cancer cell proliferation and epithelial-to-mesenchymal transition via downregulation of miR-99b and miR-192[J]. Biomed Pharmacother, 2018, 101: 656-662. DOI: 10.1016/j.biopha.2018.02.113.
    [19] WANG XZ, WU WF. Correlation of the expressions of miR-155 and suppressor of cytokine signaling 1 mRNA in peripheral blood mononuclear cells with the degree of liver injury in patients with chronic hepatitis B[J/CD]. Chin J Liver Dis(Electronic Edition), 2019, 11(3): 14-20. DOI: 10.3969/j.issn.1674-7380.2019.03.003.

    汪增秀, 吴卫锋. 慢性乙型肝炎患者外周血单个核细胞中miR-155和细胞因子信号转导抑制分子1相对表达量与肝功能损伤程度的相关性[J/CD]. 中国肝脏病杂志(电子版), 2019, 11(3): 14-20. DOI: 10.3969/j.issn.1674-7380.2019.03.003.
    [20] SHAO MF, ZOU JA, YU ZQ, et al. Expression and clinical significance of miR-21 in peripheral blood mononuclear cells of patients with prostate cancer[J]. Chin J Med Offic, 2019, 47(8): 799-801, 803. DOI: 10.16680/j.1671-3826.2019.08.09.

    邵明峰, 邹建安, 余子强, 等. 前列腺癌患者外周血单个核细胞中miR-21表达及临床意义[J]. 临床军医杂志, 2019, 47(8): 799-801, 803. DOI: 10.16680/j.1671-3826.2019.08.09.
  • 加载中
图(1) / 表(3)
计量
  • 文章访问数:  425
  • HTML全文浏览量:  85
  • PDF下载量:  21
  • 被引次数: 0
出版历程
  • 收稿日期:  2020-11-02
  • 录用日期:  2020-12-03
  • 出版日期:  2021-05-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回