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血浆胆汁酸在肝肿瘤中的差异分析及应用价值

贾茹 张平平 袁苑 胡义扬 冯琴

引用本文:
Citation:

血浆胆汁酸在肝肿瘤中的差异分析及应用价值

DOI: 10.12449/JCH241018
基金项目: 

国家自然科学基金 (82104619);

上海市卫健委卫生行业临床研究专项 (20214Y0455);

上海中医药大学预算内项目 (2021LK105)

伦理学声明:本研究方案经由上海中医药大学附属曙光医院伦理委员会审批,批号:2020-831-38-01。
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:贾茹负责实验设计,样本采集,数据分析及论文撰写;张平平、袁苑负责样本采集及数据分析;胡义扬负责指导实验设计;冯琴负责指导实验设计及论文撰写并最终定稿。
详细信息
    通信作者:

    冯琴, fengqin@shutcm.edu.cn (ORCID: 0000-0002-4641-1636)

Differences and application value of plasma bile acids in tumors of the liver

Research funding: 

National Natural Science Foundation of China (82104619);

Shanghai Municipal Health Commission Health Industry Clinical Research Project (20214Y0455);

Project under Budget of Shanghai University of Traditional Chinese Medicine (2021LK105)

More Information
  • 摘要:   目的  分析原发性肝癌与转移性肝癌患者血浆胆汁酸水平及其与临床指标的相关性,并评估其联合AFP对于原发性肝癌的诊断价值。  方法  纳入2020年8月—2021年9月于上海中医药大学附属曙光医院就诊且具有组织病理学及影像学明确的75例原发性肝癌患者及79例转移性肝癌患者,采集外周血并分别分离血清及血浆,比色法及色谱法检测生化指标,电化学发光免疫分析法检测肿瘤标志物水平,高效液相色谱-串联质谱法检测胆汁酸含量。符合正态分布的计量资料两组间比较采用成组t检验,不符合正态分布的计量资料两组间比较采用Mann-Whitney U检验。相关性检验采用Spearman相关分析。临床诊断效能采用受试者工作特征曲线(ROC曲线)评估。  结果  原发性肝癌组患者TC、TG、LDL-C及载脂蛋白(Apo)B显著低于转移性肝癌组患者,差异均具有统计学意义(U值分别为1 598、1 255、909、889,P值均<0.05)。原发性肝癌组患者AFP显著高于转移性肝癌组患者,癌胚抗原(CEA)显著低于转移性肝癌组患者,差异均具有统计学意义(U值分别为1 873、926,P值均<0.05)。原发性肝癌组患者总胆汁酸(TBA)、胆酸(CA)、鹅脱氧胆酸(CDCA)、熊脱氧胆酸(UDCA)、牛磺胆酸(TCA)、牛磺鹅脱氧胆酸(TCDCA)、甘氨胆酸(GCA)、甘氨鹅脱氧胆酸(GCDCA)、牛磺熊脱氧胆酸(TUDCA)、甘氨熊脱氧胆酸(GUDCA)均显著高于转移性肝癌患者,脱氧胆酸(DCA)显著低于转移性肝癌患者,差异均具有统计学意义(P值均<0.05)。总人群中TBA、CDCA、GCA、GCDCA、GUDCA、TCA、TCDCA及TUDCA含量与AFP水平呈显著正相关(P值均<0.05)。原发性肝癌患者中GCA、TCA、TCDCA及TUDCA含量与AFP水平呈显著正相关(P值均<0.05)。AFP+TCA+GCA+TCDCA联合检测的AUC为0.822(95%CI:0.746~0.898,P<0.000 1),效能最高。  结论  原发性肝癌与转移性肝癌患者血浆胆汁酸含量具有显著差异,差异性胆汁酸与肝损伤及AFP升高密切相关,联合AFP对原发性肝癌具有更优的临床诊断价值。

     

  • 图  1  总人群中血浆胆汁酸含量与临床指标的相关性分析

    Figure  1.  Correlation analysis of plasma BA and clinical markers in all liver cancer patients

    图  2  原发性肝癌人群中血浆胆汁酸含量与临床指标的相关性分析

    Figure  2.  Correlation analysis of plasma BA and clinical markers in primary liver cancer patients

    图  3  AFP联合血浆胆汁酸区别原发性肝癌的ROC曲线分析

    Figure  3.  ROC curves of AFP combined with plasma BA for detection of primary liver cancer

    表  1  两组患者生化指标比较

    Table  1.   Comparison of levels of laboratory tests between patients with primary liver cancer or metastatic liver cancer

    项目 原发性肝癌组(n=75) 转移性肝癌组(n=79) 统计值 P
    ALT(U/L) 25.00(18.00~33.00) 22.00(12.00~37.00) U=2 375 0.177
    AST(U/L) 31.00(27.25~52.00) 29.00(20.75~46.00) U=1 933 0.063
    TBil(μmol/L) 20.10(13.70~30.90) 15.85(12.63~28.80) U=2 407 0.059
    GLU(mmol/L) 5.30(4.60~6.00) 5.05(4.70~6.00) U=2 636 0.925
    HbA1c(%) 5.40(4.90~6.00) 5.50(5.10~6.00) U=2 140 0.205
    TC(mmol/L) 3.87(3.31~4.58) 4.81(4.18~5.91) U=1 598 <0.001
    TG(mmol/L) 1.04(0.88~1.38) 1.31(1.07~1.85) U=1 255 <0.001
    HDL-C(mmol/L) 1.07±0.29 1.09±0.34 t=0.243 0.867
    LDL-C(mmol/L) 2.09(1.45~2.73) 3.06(2.38~4.08) U=909 <0.001
    ApoA1(g/L) 0.90(0.73~1.06) 0.93(0.81~1.14) U=1 474 0.154
    ApoB(g/L) 0.67(0.49~0.89) 0.93(0.69~1.16) U=889 <0.001
    下载: 导出CSV

    表  2  两组患者肿瘤标志物水平比较

    Table  2.   Comparison of levels of serum tumor markers between patients with primary liver cancer or metastatic liver cancer

    项目 原发性肝癌组(n=75) 转移性肝癌组(n=79) U P
    AFP(ng/mL) 6.45(3.16~15.74) 4.02(2.54~5.23) 1 873 <0.001
    CEA(ng/mL) 3.04(2.53~5.42) 15.14(5.02~83.18) 926 <0.001
    CA19-9(U/mL) 21.20(10.83~54.69) 21.36(10.22~154.38) 2 361 0.840
    CA125(U/mL) 18.70(12.50~36.20) 21.20(10.55~44.63) 1 181 0.128
    下载: 导出CSV

    表  3  两组患者血浆胆汁酸含量比较

    Table  3.   Comparison of concentrations of plasma BA between patients with primary liver cancer or metastatic liver cancer

    项目 原发性肝癌组(n=75) 转移性肝癌组(n=79) U P
    TBA(nmol/L) 11 675.7(6 098.5~33 679.9) 5 241.6(2 445.8~10 062.8) 886 <0.001
    CA(nmol/L) 290.7(148.6~1 030.0) 114.0(62.8~319.0) 1 084 <0.001
    CDCA(nmol/L) 2 570.0(766.4~3 040.0) 527.0(191.5~1 127.2) 750 <0.001
    DCA(nmol/L) 66.9(6.9~354.0) 238.3(19.1~572.0) 1 223 0.010
    UDCA(nmol/L) 199.0(109.5~572.5) 68.7(26.8~246.5) 1 039 <0.001
    LCA(nmol/L) 15.7(6.3~45.6) 21.2(10.7~39.9) 1 476 0.243
    TCA(nmol/L) 444.0(90.3~2 231.1) 47.2(11.3~482.2) 862 <0.001
    TCDCA(nmol/L) 627.0(256.0~5 060.0) 145.0(48.7~981.9) 828 <0.001
    GCA(nmol/L) 1 309.2(424.0~4 670.0) 444.6(190.5~1 400.4) 1 018 <0.001
    GCDCA(nmol/L) 3 530.0(1 160.0~13 341.0) 1 149.3(388.4~3 537.4) 978 <0.001
    TDCA(nmol/L) 23.6(0.0~114.0) 25.6(5.0~92.3) 1 423 0.144
    TUDCA(nmol/L) 41.8(10.8~117.0) 7.3(1.9~21.5) 832 <0.001
    TLCA(nmol/L) 0.9(0.2~4.0) 0.9(0.0~2.3) 1 520 0.352
    GDCA(nmol/L) 119.8(5.9~609.0) 187.0(13.7~498.0) 1 586 0.570
    GUDCA(nmol/L) 434.0(156.8~1 390.0) 104.0(49.9~637.1) 986 <0.001
    GLCA(nmol/L) 5.2(0.6~29.0) 6.4(1.8~19.8) 1 641 0.789
    下载: 导出CSV
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