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血清细胞角质素片段19在胃癌患者中的表达及对HER-2阳性的预测能力

张旭 南京柱 栾小娟 张庆

张旭, 南京柱, 栾小娟, 张庆. 血清细胞角质素片段19在胃癌患者中的表达及对HER-2阳性的预测能力[J]. 解放军医学院学报, 2023, 44(5): 495-500. doi: 10.3969/j.issn.2095-5227.2023.05.010
引用本文: 张旭, 南京柱, 栾小娟, 张庆. 血清细胞角质素片段19在胃癌患者中的表达及对HER-2阳性的预测能力[J]. 解放军医学院学报, 2023, 44(5): 495-500. doi: 10.3969/j.issn.2095-5227.2023.05.010
ZHANG Xu, NAN Jingzhu, LUAN Xiaojuan, ZHANG Qing. Expression of serum keratin fragment 19 in patients with gastric cancer and its predictive power for positive HER-2[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2023, 44(5): 495-500. doi: 10.3969/j.issn.2095-5227.2023.05.010
Citation: ZHANG Xu, NAN Jingzhu, LUAN Xiaojuan, ZHANG Qing. Expression of serum keratin fragment 19 in patients with gastric cancer and its predictive power for positive HER-2[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2023, 44(5): 495-500. doi: 10.3969/j.issn.2095-5227.2023.05.010

血清细胞角质素片段19在胃癌患者中的表达及对HER-2阳性的预测能力

doi: 10.3969/j.issn.2095-5227.2023.05.010
详细信息
    作者简介:

    张旭,男,在读硕士,技师。研究方向:消化病学。Email: zhangxudhr@126.com

    通讯作者:

    张庆,女,博士,副教授。Email: zqy6920@sina.com

  • 中图分类号: R735.2

Expression of serum keratin fragment 19 in patients with gastric cancer and its predictive power for positive HER-2

More Information
  • 摘要:   背景  HER-2阳性的胃癌患者预后较差,且缺少与胃癌HER-2阳性相关肿瘤标志物的报道。  目的  探讨血清CYFRA21-1表达水平与HER-2阳性胃癌患者的相关性。  方法  收集2019年1月 - 2021年12月在解放军总医院手术治疗的胃癌患者165例,其中男115例,女50例,年龄29 ~ 82岁。分析HER-2基因表达阳性患者的CYFRA21-1水平,并绘制CYFRA21-1在HER-2阳性患者中表达的ROC曲线,分析其预测HER-2阳性胃癌的阈值。  结果  血清CYFRA21-1水平与胃癌的病理组织学分化程度和分型、TNM分期及肿瘤大小有关(P<0.05);HER-2阳性组中CYFRA21-1水平显著高于阴性组(P=0.038);CYFRA21-1阳性表达在HER-2阳性组中的OR值为3.529(95% CI:0.967 ~ 12.878),对HER-2阳性胃癌患者的预测百分比为70.4%,当CYFRA21-1的Cut-off值为3.62 ng/mL时,对胃癌患者HER-2阳性的预测敏感度和特异度达到最高,分别为0.552和0.833。CYFRA21-1<3.62 ng/mL的胃癌患者1年、2年、3年生存率高于CYFRA21-1>3.62 ng/mL者(P=0.002),HER-2阴性胃癌患者1年、2年、3年生存率高于阳性者(P=0.044)。  结论  HER-2基因及血清CYFRA21-1水平在胃癌转移、肿瘤较大、TNM分期较晚的患者中表达升高。CYFRA21-1水平较高、HER-2阳性者生存预后较差。高血清CYFRA21-1水平对胃癌患者HER-2基因阳性表达有一定的预测价值。

     

  • 图  1  肿瘤标志物预测HER-2阳性胃癌患者的ROC曲线

    Figure  1.  ROC curves of tumor marker prediction in patients with HER-2 positive gastric cancer

    图  2  不同CYFRA21-1水平及HER-2表达胃癌患者的生存曲线

    Figure  2.  Survival curves of gastric cancer patients with different CYFRA21-1 levels and HER-2 expression

    表  1  HER-2阳性和阴性患者的临床基线资料及患者不同状态下HER-2表达(例,%)、CYFRA21-1水平[Md(IQR)]差异比较

    Table  1.   Baseline data of patients with positive or negative HER-2 and comparison of HER-2 expression (n, %) and CYFRA21-1 level (Md[IQR]) in patients under different conditions

     分组总数/例HER-2CYFRA211/(ng·mL-1)
    阴性(n=51)阳性(n=76)χ2P水平U/HP
    性别1.9280.165-0.7380.460
     男115 40(38.26)51(44.35)2.95(2.35 ~ 5.89)
     女5011(22.00)25(50.00)3.93(2.29 ~ 6.23)
    年龄0.3970.529-0.7000.484
     <60岁6923(33.33)30(43.48)2.76(1.92 ~ 5.82)
     ≥60岁9628(29.17)46(47.92)3.00(2.35 ~ 4.44)
    分化程度0.3780.539-2.0310.042
     高-中分化腺癌7422(29.73)37(50.00)2.56(1.98 ~ 4.45)
     低分化腺癌-印戒细胞癌8929(32.58)39(43.82)3.25(2.41 ~ 4.50)
    Lauren分型0.2320.630-0.6270.530
     肠型5623(41.07)31(55.36)2.83(2.24 ~ 4.73)
     弥散型 + 混合型9028(31.11)45(50.00)3.14(2.37 ~ 4.48)
    Borrmann分型4.6510.031-0.1170.907
     早癌 + 结节型5512(21.82)32(58.18)2.81(2.44 ~ 5.66)
     溃疡型 + 弥漫型110 39(35.45)44(40.00)3.21(2.28 ~ 4.45)
    TNM分期1.9840.37111.2910.004
     Ⅰ5417(31.48)26(48.15)2.54(2.00 ~ 2.98)
     Ⅱ+Ⅲ6326(41.27)29(46.03)3.25(2.38 ~ 5.74)
     Ⅳ347(20.59)16(47.06)4.09(3.22 ~ 6.79)
    浸润程度(T)2.5210.4719.0770.028
     黏膜层5012(24.00)26(52.00)2.56(2.05 ~ 2.87)
     固有肌层156(40.00)6(40.00)3.21(1.76 ~ 5.66)
     浆膜层4416(36.36)19(43.18)3.00(2.29 ~ 4.50)
     胃壁全层3415(44.12)17(50.00)4.09(3.29 ~ 6.79)
    淋巴结转移(N)5.1310.274-3.513<0.001
     无6925(36.23)32(46.38)2.52(1.92 ~ 3.16)
     有7424(32.43)33(44.59)3.80(2.56 ~ 6.38)
    远处转移(M)1.8240.177-3.320<0.001
     无118 43(36.44)54(45.76)2.70(2.23 ~ 4.27)
     有357(20.00)17(48.57)4.44(3.60 ~ 6.84)
    肿瘤个数1.0470.306-1.1720.241
     单个133 47(35.34)61(45.86)3.10(2.36 ~ 4.45)
     多个102(20.00)6(60.00)2.34(1.66 ~ 7.21)
    肿瘤大小0.0760.782-4.111<0.001
     直径<3 cm8628(32.56)40(46.51)2.56(1.97 ~ 3.14)
     直径≥3 cm5621(37.50)27(48.21)4.38(3.25 ~ 6.78)
    下载: 导出CSV

    表  2  肿瘤标志物水平在HER-2阳性与阴性胃癌患者中的表达差异[Md(IQR)]

    Table  2.   Differences in the expression of tumor markers levels in patients with HER-2 positive or negative gastric cancer (Md[IQR])

     变量HER-2阴性
    (n=51)
    HER-2阳性
    (n=76)
    UP
    CEA/(μg·L-1)2.39(1.60 ~ 3.37)2.80(1.36 ~ 5.73)-1.8100.070
    AFP/(μg·L-1)2.97(1.93 ~ 3.78)2.67(2.37 ~ 3.03)-0.2340.815
    CA19-9/(U·mL-1)8.87(6.38 ~ 11.11)10.25(6.30 ~ 25.34)-1.1950.232
    CA15-3/(U·mL-1)7.65(6.37 ~ 10.94)9.34(6.81 ~ 12.45)-1.8200.069
    CA724/(U·mL-1)2.35(1.20 ~ 3.99)3.19(1.41 ~ 9.96)-1.0060.314
    CYFRA21-1/(ng·mL-1)2.38(2.20 ~ 3.38)3.91(2.57 ~ 6.60)-2.0730.038
    NSE/(ng·mL-1)11.66(9.84 ~ 16.53)12.50(9.48 ~ 15.24)-0.9090.364
    SCC/(ng·mL-1)0.90(0.70 ~ 1.30)0.85(0.70 ~ 1.03)-0.1560.876
    PGⅠ/(ng·mL-1)47.10(29.00 ~ 73.80)53.80(33.80 ~ 111.88)-1.0090.313
    PGⅡ/(ng·mL-1)10.40(7.00 ~ 15.90)15.55(8.50 ~ 23.73)-1.4460.148
    PGⅠ/Ⅱ5.79(2.64 ~ 7.67)4.03(2.39 ~ 6.34)-0.8950.371
    下载: 导出CSV

    表  3  HER-2表达与CYFRA21-1水平相关性分析

    Table  3.   Correlation analysis of HER-2 expression and CYFRA21-1 level

     变量CYFRA21-1
    rP
    HER-20.2510.037
    下载: 导出CSV

    表  4  基于CYFRA211、CEA、CA153建立的二元logistic回归模型

    Table  4.   Binary logistic regression model based on CYFRA211

     变量B$S \bar x $WaldSigOROR 95% CI
    CYFRA2111.2610.6613.6440.0563.5290.967 ~ 12.878
    CEA0.8590.9450.8250.3642.3600.370 ~ 15.049
    CA1530.9981.2400.6480.4212.7130.239 ~ 30.828
    常数-0.0230.3220.0050.9440.978-
    下载: 导出CSV

    表  5  血清肿瘤标志物预测HER-2阳性胃癌患者的效能

    Table  5.   Efficacy of serum tumor markers in predicting HER-2 positive gastric cancer patients

     变量敏感
    特异
    约登
    指数
    截断
    PAUC95% CI
    CEA0.3100.9440.2554.250.4700.5630.399 ~ 0.727
    AFP0.8970.3330.2302.030.5840.4520.264 ~ 0.640
    CA19-90.3100.9440.25520.950.2940.5920.431 ~ 0.753
    CA15-30.6900.5560.2457.720.4060.5730.406 ~ 0.740
    CA7240.4140.8890.3035.570.1650.6220.459 ~ 0.784
    NSE0.5860.6110.19712.170.9650.4960.317 ~ 0.675
    SCC0.6900.3890.0790.800.4700.4370.264 ~ 0.609
    PGⅠ0.3450.8890.23488.700.3750.5780.407 ~ 0.748
    PGⅡ0.5860.7220.30814.000.1890.6150.445 ~ 0.785
    PGⅠ/Ⅱ0.7930.2780.0712.720.3360.4160.243 ~ 0.588
    CYFRA21-10.5520.8330.3853.620.0200.7040.548 ~ 0.860
    下载: 导出CSV
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出版历程
  • 收稿日期:  2022-07-29
  • 网络出版日期:  2023-05-12
  • 刊出日期:  2023-05-28

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