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胆管癌和胆总管结石患者胆汁中钙卫蛋白检测的临床意义

计婷婷 白冰清 崔喻芳 汪少飞 洪江龙 李扬 鲍峻峻 梅俏

引用本文:
Citation:

胆管癌和胆总管结石患者胆汁中钙卫蛋白检测的临床意义

DOI: 10.12449/JCH240321
基金项目: 

安徽省自然科学基金青年项目 (2008085QH415)

伦理学声明:本研究于2019年10月15日经安徽医科大学第一附属医院伦理委员会批准(批号:PJ2018-12-17),入组患者均签署知情同意书。
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:计婷婷、白冰清负责课题设计,资料分析,撰写论文;崔喻芳、汪少飞、洪江龙、李扬、鲍峻峻参与收集数据,修改论文;梅俏负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    梅俏, meiqiaomq@aliyun.com (ORCID: 0000-0002-0635-6564)

Clinical significance of determining the level of biliary calprotectin in patients with cholangiocarcinoma or choledocholithiasis

Research funding: 

Youth Project of Natural Science Foundation of Anhui Province (2008085QH415)

More Information
  • 摘要:   目的  探讨胆管癌和胆总管结石患者胆汁中钙卫蛋白水平的差异。  方法  收集2021年5月—2022年9月安徽医科大学第一附属医院行ERCP诊治的胆管癌(n=34)和胆总管结石(n=78)患者的临床资料和胆汁标本。采用荧光免疫层析法检测胆汁中钙卫蛋白、血红蛋白和乳铁蛋白水平。计量资料两组间比较采用Mann-Whitney U检验;计数资料两组间比较采用χ2检验;相关分析采用Spearman相关性检验;DeLong检验比较不同受试者工作特征曲线(ROC曲线)下面积(AUC)的差异。  结果  与胆总管结石组比较,胆管癌患者胆汁中钙卫蛋白水平升高[4 795.50(2 286.79~20 179.73)ng/mL vs 411.16(67.03~1 991.88)ng/mL,Z=5.572,P<0.001],同时氯化物水平升高[115.70(109.10~125.50)mmol/L vs 106.60(98.60~114.40)mmol/L,Z=2.702,P=0.007]。进一步将胆管癌分为高位胆管癌和低位胆管癌,两组钙卫蛋白比较差异无统计学意义[3 867.71(2 235.66~26 407.40)ng/mL vs 4 795.50(2 361.15~13 070.53)ng/mL,Z=0.129,P>0.05]。胆汁钙卫蛋白水平与胆汁白细胞计数、血红蛋白、乳铁蛋白水平具有相关性(r值分别为0.316、0.353、0.464,P值均<0.05)。ROC曲线结果示胆汁钙卫蛋白(敏感度79.4%,特异度75.6%)、血CA19-9水平(敏感度82.4%,特异度78.2%)以及两者联合(敏感度88.2%,特异度73.1%)对诊断胆管癌具有良好的敏感性和特异性。  结论  胆管癌患者胆汁中钙卫蛋白水平升高,可能成为胆管癌诊断的生物标志物。

     

  • 图  1  胆管癌患者胆汁中钙卫蛋白等指标的预测作用

    Figure  1.  Predictive effect of calprotectin level in bile of patients with cholangiocarcinoma

    表  1  胆管癌组与胆总管结石组患者临床资料比较

    Table  1.   Clinical data of patients with cholangiocarcinoma and cholangiolithiasis

    项目 胆总管结石组(n=78) 胆管癌组(n=34) 统计值 P
    男/女(例) 40/38 19/15 χ2=0.201 0.654
    年龄(岁) 68.50(56.00~77.25) 73.50(69.00~80.00) Z=2.321 0.020
    WBC(×109/L) 5.84(4.65~7.78) 7.51(5.38~10.16) Z=2.082 0.037
    NEU(%) 66.50(50.73~77.75) 79.70(68.35~89.35) Z=4.028 <0.001
    血红蛋白(g/L) 122.00±14.76 102.76±18.25 Z=5.169 <0.001
    Alb(g/L) 38.33±4.70 32.33±5.31 Z=5.044 <0.001
    TBil(μmol/L) 19.59(12.70~42.40) 152.13(49.18~271.88) Z=5.588 <0.001
    ALT(U/L) 46.50(21.75~150.50) 88.00(61.50~194.75) Z=2.721 0.006
    AST(U/L) 35.00(23.00~97.75) 124.00(66.50-220.75) Z=4.531 <0.001
    ALP(U/L) 154.00(94.00~248.25) 627.00(330.25~1 019.25) Z=6.056 <0.001
    AFP(ng/mL) 2.08(1.38~3.04) 1.87(1.30~2.86) Z=0.940 0.347
    CEA(ng/mL) 1.46(0.73~2.53) 2.36(1.46~6.16) Z=3.163 0.002
    CA19-9(U/mL) 17.80(8.66~47.80) 342.34(127.99~1 000.00) Z=5.126 <0.001
    下载: 导出CSV

    表  2  胆管癌组与胆总管结石组患者胆汁常规和生化检查结果

    Table  2.   Routine and biochemical examination of bile in patients with cholangiocarcinoma and cholangiolithiasis

    项目 胆总管结石组(n=78) 胆管癌组(n=34) Z P
    WBC(×106/L) 7.00(2.00~59.00) 22.50(2.75~60.50) 0.847 0.397
    RBC(×106/L) 0.00(0.00~58.00) 17.00(0.00~637.50) 1.473 0.141
    多个核细胞百分比(%) 70.40(28.60~100.00) 71.40(42.50~93.10) 0.297 0.766
    氯化物(mmol/L) 106.60(98.60~114.40) 115.70(109.10~125.50) 2.702 0.007
    葡萄糖(mmol/L) 0.07(0.01~0.45) 0.01(0.01~0.14) 1.254 0.210
    蛋白(g/L) 0.15(0.10~3.25) 1.00(0.10~4.30) 1.206 0.228
    LDH(U/L) 73.50(36.50~157.50) 99.00(58.00~437.00) 1.273 0.203
    下载: 导出CSV

    表  3  胆管癌组与胆总管结石组患者胆汁钙卫蛋白等水平检测

    Table  3.   Determination of calprotectin and other substances in bile of cholangiocarcinoma and cholangiolithiasis patients

    项目 胆总管结石组(n=78) 胆管癌组(n=34) Z P
    钙卫蛋白(ng/mL) 411.16(67.03~1 991.88) 4 795.50(2 286.79~20 179.73) 5.572 <0.001
    血红蛋白(ng/mL) 6 338.13(1 430.09~27 453.84) 14 100.82(713.08~44 695.15) 1.006 0.314
    乳铁蛋白(ng/mL) 478.79(184.75~1 319.59) 523.19(224.53~3 526.59) 1.174 0.240
    下载: 导出CSV

    表  4  胆管癌患者胆汁中钙卫蛋白等指标的预测作用

    Table  4.   Predictive effect of calprotectin level in bile of patients with cholangiocarcinoma

    项目 AUC P 截断值 敏感度 特异度 阳性预测值 阴性预测值
    钙卫蛋白 0.832 <0.001 1 977.17 0.794 0.756 0.587 0.894
    血红蛋白 0.560 0.314 19 001.22 0.471 0.718
    乳铁蛋白 0.570 0.240 2 258.57 0.324 0.859
    血CA19-9 0.805 <0.001 55.47 0.824 0.782 0.622 0.910
    钙卫蛋白+CA19-9 0.855 <0.001 0.19 0.882 0.731 0.588 0.934
    下载: 导出CSV
  • [1] RAGGI C, TADDEI ML, RAE C, et al. Metabolic reprogramming in cholangiocarcinoma[J]. J Hepatol, 2022, 77( 3): 849- 864. DOI: 10.1016/j.jhep.2022.04.038.
    [2] JANG S, STEVENS T, KOU L, et al. Efficacy of digital single-operator cholangioscopy and factors affecting its accuracy in the evaluation of indeterminate biliary stricture[J]. Gastrointest Endosc, 2020, 91( 2): 385- 393.e1. DOI: 10.1016/j.gie.2019.09.015.
    [3] CHEN S, WANG J. Advances in tumor microenvironment and immunotherapy of cholangiocarcinoma[J]. J Clin Hepatol, 2022, 38( 10): 2428- 2432. DOI: 10.3969/j.issn.1001-5256.2022.10.044.

    陈顺, 王俊. 胆管癌肿瘤微环境与免疫治疗[J]. 临床肝胆病杂志, 2022, 38( 10): 2428- 2432. DOI: 10.3969/j.issn.1001-5256.2022.10.044.
    [4] ZUO S, CHEN Q, ZOU WL. Current status and prospect of immunotherapy for cholangiocarcinoma[J]. Chin J Dig Surg, 2022, 21( 7): 873- 879. DOI: 10.3760/cma.j.cn115610-20220506-00254.

    左石, 陈乾, 邹卫龙. 胆管癌免疫治疗的现状与展望[J]. 中华消化外科杂志, 2022, 21( 7): 873- 879. DOI: 10.3760/cma.j.cn115610-20220506-00254.
    [5] GIESE MA, HIND LE, HUTTENLOCHER A. Neutrophil plasticity in the tumor microenvironment[J]. Blood, 2019, 133( 20): 2159- 2167. DOI: 10.1182/blood-2018-11-844548.
    [6] JUKIC A, BAKIRI L, WAGNER EF, et al. Calprotectin: From biomarker to biological function[J]. Gut, 2021, 70( 10): 1978- 1988. DOI: 10.1136/gutjnl-2021-324855.
    [7] ARGYRIS PP, SLAMA ZM, ROSS KF, et al. Calprotectin and the initiation and progression of head and neck cancer[J]. J Dent Res, 2018, 97( 6): 674- 682. DOI: 10.1177/0022034518756330.
    [8] SHABANI F, FARASAT A, MAHDAVI M, et al. Calprotectin(S100A8/S100A9): A key protein between inflammation and cancer[J]. Inflamm Res, 2018, 67( 10): 801- 812. DOI: 10.1007/s00011-018-1173-4.
    [9] PAN SG, HU Y, HU MJ, et al. S100A8 facilitates cholangiocarcinoma metastasis via upregulation of VEGF through TLR4/NF-‍κB pathway activation[J]. Int J Oncol, 2020, 56( 1): 101- 112. DOI: 10.3892/ijo.2019.4907.
    [10] LIANG HJ, QIN SK, SHEN F, et al. Expert consensus on diagnosis and treatment of CSCO biliary systerm tumors(2019 edition)[J]. Chin Clin Oncol, 2019, 24( 9): 828- 838.

    梁后杰, 秦叔逵, 沈锋, 等. CSCO胆道系统肿瘤诊断治疗专家共识(2019年版)[J]. 临床肿瘤学杂志, 2019, 24( 9): 828- 838.
    [11] DELONG ER, DELONG DM, CLARKE-PEARSON DL. Comparing the areas under two or more correlated receiver operating characteristic curves: A nonparametric approach[J]. Biometrics, 1988, 44( 3): 837- 845.
    [12] KHAN SA, DAVIDSON BR, GOLDIN RD, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: An update[J]. Gut, 2012, 61( 12): 1657- 1669. DOI: 10.1136/gutjnl-2011-301748.
    [13] CAO HS, HUANG T, DAI MR, et al. Tumor microenvironment and its implications for antitumor immunity in cholangiocarcinoma: Future perspectives for novel therapies[J]. Int J Biol Sci, 2022, 18( 14): 5369- 5390. DOI: 10.7150/ijbs.73949.
    [14] MAO ZY, ZHU GQ, XIONG M, et al. Prognostic value of neutrophil distribution in cholangiocarcinoma[J]. World J Gastroenterol, 2015, 21( 16): 4961- 4968. DOI: 10.3748/wjg.v21.i16.4961.
    [15] ZHOU SL, DAI Z, ZHOU ZJ, et al. CXCL5 contributes to tumor metastasis and recurrence of intrahepatic cholangiocarcinoma by recruiting infiltrative intratumoral neutrophils[J]. Carcinogenesis, 2014, 35( 3): 597- 605. DOI: 10.1093/carcin/bgt397.
    [16] LI YW, QIU SJ, FAN J, et al. Intratumoral neutrophils: A poor prognostic factor for hepatocellular carcinoma following resection[J]. J Hepatol, 2011, 54( 3): 497- 505. DOI: 10.1016/j.jhep.2010.07.044.
    [17] JENSEN HK, DONSKOV F, MARCUSSEN N, et al. Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma[J]. J Clin Oncol, 2009, 27( 28): 4709- 4717. DOI: 10.1200/JCO.2008.18.9498.
    [18] JAILLON S, PONZETTA A, DI MITRI D, et al. Neutrophil diversity and plasticity in tumour progression and therapy[J]. Nat Rev Cancer, 2020, 20( 9): 485- 503. DOI: 10.1038/s41568-020-0281-y.
    [19] SHAUL ME, FRIDLENDER ZG. Tumour-associated neutrophils in patients with cancer[J]. Nat Rev Clin Oncol, 2019, 16( 10): 601- 620. DOI: 10.1038/s41571-019-0222-4.
    [20] VOIGTLÄNDER T, WLECKE J, NEGM AA, et al. Calprotectin in bile: A disease severity marker in patients with primary sclerosing cholangitis[J]. J Clin Gastroenterol, 2014, 48( 10): 866- 869. DOI: 10.1097/MCG.0000000000000042.
    [21] GAUSS A, SAUER P, STIEHL A, et al. Evaluation of biliary calprotectin as a biomarker in primary sclerosing cholangitis[J]. Medicine, 2016, 95( 17): e3510. DOI: 10.1097/MD.0000000000003510.
    [22] SRIKRISHNA G. S100A8 and S100A9: New insights into their roles in malignancy[J]. J Innate Immun, 2012, 4( 1): 31- 40. DOI: 10.1159/000330095.
    [23] JAMNONGKAN W, THANAN R, TECHASEN A, et al. Upregulation of transferrin receptor-1 induces cholangiocarcinoma progression via induction of labile iron pool[J]. Tumour Biol, 2017, 39( 7): 1010428317717655. DOI: 10.1177/1010428317717655.
    [24] MANCINELLI R, CUTONE A, ROSA L, et al. Different iron-handling in inflamed small and large cholangiocytes and in small and large-duct type intrahepatic cholangiocarcinoma[J]. Eur J Histochem, 2020, 64( 4): 3156. DOI: 10.4081/ejh.2020.3156.
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  • 收稿日期:  2023-06-16
  • 录用日期:  2023-07-14
  • 出版日期:  2024-03-20
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