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BTLA、CTLA-4基因多态性与肝癌TACE联合靶向治疗疗效及预后相关性

陆小华 袁洪新

陆小华, 袁洪新. BTLA、CTLA-4基因多态性与肝癌TACE联合靶向治疗疗效及预后相关性[J]. 昆明医科大学学报, 2023, 44(9): 126-135. doi: 10.12259/j.issn.2095-610X.S20230927
引用本文: 陆小华, 袁洪新. BTLA、CTLA-4基因多态性与肝癌TACE联合靶向治疗疗效及预后相关性[J]. 昆明医科大学学报, 2023, 44(9): 126-135. doi: 10.12259/j.issn.2095-610X.S20230927
Xiaohua LU, Hongxin YUAN. The Analysis of the Correlation between BTLA,CTLA-4 Gene Polymorphisms and the Efficacy and Prognosis of TACE Combined Targeted Therapy for Liver Cancer[J]. Journal of Kunming Medical University, 2023, 44(9): 126-135. doi: 10.12259/j.issn.2095-610X.S20230927
Citation: Xiaohua LU, Hongxin YUAN. The Analysis of the Correlation between BTLA,CTLA-4 Gene Polymorphisms and the Efficacy and Prognosis of TACE Combined Targeted Therapy for Liver Cancer[J]. Journal of Kunming Medical University, 2023, 44(9): 126-135. doi: 10.12259/j.issn.2095-610X.S20230927

BTLA、CTLA-4基因多态性与肝癌TACE联合靶向治疗疗效及预后相关性

doi: 10.12259/j.issn.2095-610X.S20230927
基金项目: 南通市科技局基础科学研究公众健康基金资助项目(JC2021196)
详细信息
    作者简介:

    陆小华(1982~),男,江苏南通人,医学硕士,副主任医师,主要从事肿瘤及血管相关疾病的介入治疗及机制研究工作

    通讯作者:

    袁洪新,E-mail:jopx6087@21cn.com

  • 中图分类号: R735.7

The Analysis of the Correlation between BTLA,CTLA-4 Gene Polymorphisms and the Efficacy and Prognosis of TACE Combined Targeted Therapy for Liver Cancer

  • 摘要:   目的   探讨B及T淋巴细胞弱化因子(BTLA)、细胞毒性T淋巴细胞抗原-4(CTLA-4)基因多态性与肝癌经动脉插管化疗栓塞(TACE)联合靶向治疗疗效及预后相关性。  方法   选取2021年1月至2021年12月期间南通大学附属医院介入放射科收治的新发85例肝癌患者作为研究对象,均行TACE联合靶向治疗,根据RECIST实体瘤疗效评价标准将患者分为治疗有效组(n = 58)、疾病进展组(n = 27),比较2组临床资料、BTLA、CTLA-4基因多态性,分析BTLA、CTLA-4基因多态性与疗效的相关性,并于治疗后18个月电话随访生存状况,对比不同基因型患者生存状况,分析其与生存预后的相关性。  结果   CTLA-4 rs231775、rs733618、rs3087243、rs4553808位点、BTLA rs2171513、rs3112270、rs1982809、rs16859629位点基因型均符合Hardy-Weinberg遗传平衡定律;治疗有效组BTLA rs3112270位点AG、GG基因型比例、rs1982809位点GA、AA比例、rs16859629位点CC基因型、CTLA-4 rs231775位点AA基因型比例、rs3087243位点GA、AA基因型低于疾病进展组,BTLA rs3112270位点AA基因型比例、rs1982809位点GG比例、rs16859629位点TT基因型、CTLA-4 rs231775位点GG基因型比例、rs3087243位点GG基因型高于疾病进展组(P < 0.05);单因素、多因素分析显示,BTLA rs3112270 A > G、rs1982809 G > A、rs16859629 T > C、CTLA-4 rs231775 A > G、rs3087243 G > A与疗效相关(P < 0.05);BTLA rs3112270位点AA、AG基因型患者18个月生存率高于GG基因型患者,rs1982809位点GG、GA基因型患者18个月生存率高于AA基因型患者,rs16859629位点TT基因型患者18个月生存率高于TC、CC基因型患者(P < 0.05);CTLA-4 rs231775位点GG、GA基因型患者18个月生存率高于AA基因型患者、rs3087243位点GG基因型18个月生存率高于GA、AA基因型患者(P < 0.05);单因素、多因素分析显示,BTLA rs3112270 A > G、rs1982809 G > A、rs16859629 T > C、CTLA-4 rs231775 A > G、rs3087243 G > A与生存预后相关(P < 0.05)。  结论   BTLA基因rs3112270、rs1982809、rs16859629、CTLA-4基因rs231775、rs3087243位点多态性与肝癌TACE联合靶向治疗疗效、预后密切相关,以期为预估TACE治疗提供参考。
  • 图  2  不同CTLA-4位点基因型患者生存曲线

    Figure  2.  Survival curves of patients with different CTLA-4 genotypes

    图  1  不同BTLA位点基因型患者生存曲线

    Figure  1.  Survival curves of patients with different BTLA loci genotypes

    表  1  2组临床资料比较[n(%)/($\bar{x} \pm s$)]

    Table  1.   Comparison of clinical data between two groups [n(%)/($\bar{x} \pm s$)]

    资料治疗有效组(n = 58)疾病进展组(n = 27)t/χ2P
    性别 0.552 0.457
     男 43(74.14) 22(81.48)
     女 15(25.86) 5(18.52)
    年龄(岁) 52.13 ± 4.76 52.82 ± 5.11 0.608 0.545
    BMI(kg/m2 21.39 ± 1.25 21.18 ± 1.17 0.736 0.464
    肿瘤最大径(cm) 3.82 ± 0.51 5.03 ± 0.74 8.777 < 0.001*
    肿瘤数目(个) 2.75 ± 0.44 3.38 ± 0.53 5.753 < 0.001*
    Child-Pugh分级 5.776 0.001*
     A级 55(94.83) 20(74.07)
     B级 3(5.17) 7(25.93)
    BCLC分期 5.716 0.017*
     B期 18(31.03) 2(7.41)
     C期 40(68.97) 25(92.59)
    肝外转移 5.963 0.015*
     有 8(13.79) 10(37.04)
     无 50(86.21) 17(62.96)
    血管侵犯 4.713 0.030*
     有 24(41.38) 18(66.67)
     无 34(58.62) 9(33.33)
      *P < 0.05。
    下载: 导出CSV

    表  2  85例患者BTLA、CTLA-4基因型分布情况

    Table  2.   Distribution of BTLA and CTLA-4 genotypes in 85 patients

    BTLA基因型CTLA-4基因型
    位点n频率位点n频率
    rs2171513 rs231775
     GG 56 65.88  GG 31 36.47
     GA 25 29.41  GA 42 49.41
     AA 4 4.71  AA 12 14.12
    rs3112270 rs733618
     AA 45 52.94  CC 9 10.59
     AG 34 40.00  CT 45 52.94
     GG 6 7.06  TT 31 36.47
    rs1982809 rs3087243
     GG 48 56.47  GG 48 56.47
     GA 30 35.29  GA 32 37.65
     AA 7 8.24  AA 5 5.88
    rs16859629 rs4553808
     TT 72 84.71  AA 46 54.12
     TC 8 9.41  AG 33 38.82
     CC 5 5.88  GG 6 7.06
    下载: 导出CSV

    表  3  2组BTLA、CTLA-4基因型比较n(%)

    Table  3.   Comparison of BTLA and CTLA-4 genotypes between the two groups n(%)

    BTLA基因型CTLA-4基因型
    项目治疗有效组
    n = 58)
    疾病进展组(n = 27)uP项目治疗有效组
    n = 58)
    疾病进展组(n = 27)uP
    rs2171513 0.788 0.431 rs231775 2.920 0.004*
     GG 40(68.97) 16(59.26)  GG 25(43.10) 6(22.22)
     GA 16(27.59) 9(33.33)  GA 31(53.45) 11(40.74)
     AA 2(3.45) 2(7.41)  AA 2(3.45) 10(37.04)
    rs3112270 4.638 < 0.001* rs733618 0.019 0.945
     AA 41(70.69) 4(14.81)  CC 6(10.34) 3(11.11)
     AG 17(29.31) 17(62.96)  CT 31(53.45) 14(51.85)
     GG 0(0.00) 6(22.22)  TT 21(36.21) 10(37.04)
    rs1982809 3.347 0.001* rs3087243 4.491 < 0.001*
     GG 40(68.97) 8(29.63)  GG 43(74.14) 5(18.52)
     GA 17(29.31) 13(48.15)  GA 15(25.86) 17(62.96)
     AA 1(1.72) 6(22.22)  AA 0(0.00) 5(18.52)
    rs16859629 2.464 0.014* rs4553808 0.622 0.534
     TT 51(87.93) 16(59.26)  AA 33(56.90) 13(48.15)
     TC 7(12.07) 1(3.70)  AG 21(36.21) 12(44.44)
     CC 0(0.00) 10(37.04)  GG 4(6.90) 2(7.41)
      *P < 0.05。
    下载: 导出CSV

    表  4  BTLA、CTLA-4基因多态性与疗效的相关性

    Table  4.   Correlation between BTLA and CTLA-4 gene polymorphisms and therapeutic effect

    自变量单因素分析Logistic多因素回归分析
    OR95%CIPOR95%CIP
    BTLA基因
     rs2171513G > A 1.211 0.417~3.519 0.417 1.740 0.523~5.791 0.518
     rs3112270A > G 5.396 1.794~16.228 < 0.001* 6.252 2.041~19.153 < 0.001*
     rs1982809G > A 6.602 2.061~21.147 < 0.001* 7.699 2.274~26.065 < 0.001*
     rs16859629T > C 4.675 1.537~14.220 < 0.001* 5.441 1.882~15.730 < 0.001*
    CTLA-4基因
     rs231775A > G 5.828 1.809~18.773 < 0.001* 5.650 2.005~15.924 < 0.001*
     rs733618C > T 0.978 0.325~2.941 0.623 1.122 0.246~5.113 0.264
     rs3087243G > A 6.037 2.260~16.128 < 0.001* 6.486 2.175~19.340 < 0.001*
     rs4553808A > G 1.240 0.249~6.177 0.329 1.065 0.196~5.782 0.187
      *P < 0.05。
    下载: 导出CSV

    表  5  不同BTLA、CTLA-4基因型患者生存预后状况比较

    Table  5.   Comparison of survival and prognosis of patients with different BTLA and CTLA-4 genotypes

    BTLA基因型CTLA-4基因型
    项目n生存率χ2P项目n生存率χ2P
    rs2171513 1.115 0.543 rs231775 19.502 < 0.001*
     GG 53 71.70(38/53)  GG 30 86.67(26/30)
     GA 25 64.00(16/25)  GA 40 70.00(28/40)
     AA 4 50.00(2/4)  AA 12 16.67(2/12)
    rs3112270 11.163 0.004* rs733618 0.563 0.755
     AA 42 80.95(34/42) CC 9 66.67(6/9)
     AG 34 61.76(21/34)  CT 43 65.12(28/43)
     GG 6 16.67(1/6)  TT 30 73.33(22/30)
    rs1982809 10.928 0.004* rs3087243 22.152 < 0.001*
     GG 47 76.60(36/47)  GG 46 86.96(40/46)
     GA 28 67.86(19/28)  GA 31 51.61(16/31)
     AA 7 14.29(1/7)  AA 5 0.00(0/5)
    rs16859629 18.402 < 0.001* rs4553808 0.091 0.956
     TT 70 77.14(54/70)  AA 43 69.77(30/43)
     TC 7 28.57(2/7)  AG 33 66.67(22/33)
     CC 5 0.00(0/5)  GG 6 66.67(4/6)
      *P < 0.05。
    下载: 导出CSV

    表  6  BTLA、CTLA-4基因多态性与生存预后的相关性

    Table  6.   Correlation between BTLA and CTLA-4 gene polymorphism and survival prognosis

    自变量单因素分析Logistic多因素回归分析
    HR95%CIPHR95%CIP
    BTLA基因
     rs2171513G > A 1.156 0.187~7.144 0.095 0.902 0.165~4.936 0.236
     rs3112270A > G 4.336 1.509~12.457 < 0.001* 4.439 1.441~13.672 < 0.001*
     rs1982809G > A 5.587 1.914~16.308 < 0.001* 5.123 1.659~15.820 < 0.001*
     rs16859629T > C 6.620 2.069~21.182 < 0.001* 7.262 2.183~24.159 < 0.001*
    CTLA-4基因
     rs231775A > G 6.588 2.397~18.105 < 0.001* 6.058 2.116~17.342 < 0.001*
     rs733618C > T 1.157 0.201~6.665 0.102 0.942 0.188~4.724 0.221
     rs3087243G > A 7.906 2.522~24.781 < 0.001* 6.642 2.183~20.210 < 0.001*
     rs4553808A > G 0.907 0.194~4.238 0.174 0.834 0.176~3.952 0.279
      *P < 0.05。
    下载: 导出CSV
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出版历程
  • 收稿日期:  2023-04-13
  • 网络出版日期:  2023-09-22
  • 刊出日期:  2023-09-30

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