Changes of Immunoglobulin in TACE Treatment of Hepatocellular Carcinoma and Its Value in Predicting Curative Effect
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摘要:
目的 分析免疫球蛋白（immunoglobulin，Ig）在肝细胞性肝癌（hepatocellular carcnoma，HCC）肝动脉化疗栓塞术（transcatheter arterial chemoembolization，TACE）治疗过程中的变化及预测疗效的价值。 方法 选取2022年1月至2023年1月武警河北总队医院100例HCC患者作为肝癌组，另选50例肝脏良性疾病患者作为良性组，50例健康志愿者作为对照组。比较3组一般资料、血清Ig（IgA、IgG、IgM）及常规肿瘤标志物[甲胎蛋白（alpha feto protein，AFP）、细胞角蛋白19（cytokeratin 19，CK19）、高尔基膜蛋白73（golgi protein 73，GP73）]水平，分析肝癌组血清Ig与常规肿瘤标志物水平的相关性。并比较肝癌组TACE治疗后不同疗效患者治疗前后血清Ig、常规肿瘤标志物水平及变化值，分析血清Ig及常规肿瘤标志物水平变化值与ACE疗效的相关性、预测疗效的价值，比较含与不含Ig预测方案对疗效的预测价值。 结果 肝癌组血清IgA、IgG、IgM水平低于良性组、对照组，AFP、CK19、GP73水平高于良性组、对照组，良性组血清IgA、IgG、IgM水平低于对照组，AFP、CK19、GP73水平高于对照组（P < 0.05）；肝癌组血清IgA、IgG、IgM水平与血清AFP、CK19、GP73水平呈负相关（P < 0.05）；肝癌组TACE治疗后疗效不良患者治疗前、治疗后血清IgA、IgG、IgM水平低于疗效良好患者，AFP、CK19、GP73水平高于疗效良好患者，△IgA、△IgG、△IgM、△AFP、△CK19、△GP73小于疗效良好患者（P < 0.05）；△IgA、△IgG、△IgM、△AFP、△CK19、△GP73与TACE疗效呈正相关（P < 0.05）；△IgA、△IgG、△IgM、△AFP、△CK19、△GP73预测HCC患者TACE疗效不良的曲线下面积（AUC）分别为0.777、0.784、0.793、0.779、0.710、0.746；与不含Ig预测方案（△AFP、△CK19、△GP73联合预测）比较，含Ig预测方案（△IgA、△IgG、△IgM、△AFP、△CK19、△GP73联合预测）预测HCC患者TACE疗效不良的AUC明显增大，NRI、IDI均 > 0（P < 0.05）。 结论 HCC患者TACE治疗过程中血清IgA、IgG、IgM水平升高，各指标变化值可为临床预测TACE疗效提供可靠依据。 -
关键词:
- 肝细胞性肝癌 /
- 免疫球蛋白 /
- 肝癌肝动脉化疗栓塞术 /
- 疗效 /
- 预测
Abstract:Objective To analyze the changes of immunoglobulin （Ig） during the process of transcatheter arterial chemoembolization （TACE） for hepatocellular carcinoma （HCC） and predict the value of treatment efficacy. Methods A total of 100 HCC patients in Hebei Armed Police Corps Hospital from January 2022 to January 2023 were selected as the liver cancer group, 50 patients with benign liver disease were selected as the benign group, and 50 healthy volunteers were selected as the control group. The general data, serum Ig （IgA, IgG, IgM） and conventional tumor markers [alpha-fetoprotein （AFP）, cytokeratin 19 （CK19）, Golgi protein 73 （GP73）], and the correlation between serum Ig and conventional tumor markers in the HCC group was analyzed. The serum levels and changes of Ig and conventional tumor markers in patients with different efficacy after TACE treatment in the liver cancer group were compared before and after treatment. The correlation between the changes of serum Ig and conventional tumor markers and the efficacy of ACE was analyzed, and the predictive value of ACE prediction scheme with or without Ig was compared. Results The levels of IgA, IgG and IgM in liver cancer group were lower than those in benign group and control group; the levels of AFP, CK19 and GP73 in liver cancer group were higher than those in benign group and control group; the levels of IgA, IgG and IgM in benign group were lower than those in control group; the levels of AFP, CK19 and GP73 in benign group were higher than those in control group （P < 0.05）. Serum IgA, IgG and IgM levels were negatively correlated with serum AFP, CK19 and GP73 levels in HCC group （P < 0.05）. The serum levels of IgA, IgG and IgM in patients with poor TACE treatment were lower than those in patients with good efficacy before and after treatment, the levels of AFP, CK19 and GP73 were higher than those in patients with good efficacy, and △IgA, △IgG, △IgM, △AFP, △CK19 and △GP73 were lower than those in patients with good efficacy （P < 0.05）. △IgA, △IgG, △IgM, △AFP, △CK19, △GP73 were positively correlated with the therapeutic effect of TACE （P < 0.05）. The area under the curve （AUC） of △IgA, △IgG, △IgM, △AFP, △CK19 and △GP73 for predicting poor TACE efficacy in HCC patients were 0.777, 0.784, 0.793, 0.779, 0.710 and 0.746, respectively. Compared with the non-IG prediction scheme （△AFP, △CK19, △GP73 combined prediction）, the AUC with Ig prediction scheme （△IgA, △IgG, △IgM, △AFP, △CK19, △GP73 combined prediction） was significantly increased in predicting poor TACE efficacy in HCC patients. Both NRI and IDI were > 0 （P < 0.05）. Conclusion The levels of serum IgA, IgG and IgM in HCC patients increased during TACE treatment, and the changes of each index can provide a reliable basis for clinical prediction of TACE efficacy. -
图 1 血清Ig及常规肿瘤标志物水平变化值预测疗效的ROC曲线
Figure 1. ROC curve of serum Ig and routine tumor marker level changes to predict curative effect
图 2 含与不含Ig预测方案预测疗效的ROC曲线
Figure 2. ROC curve of predicted efficacy with and without Ig prediction regimen
表 1 3组一般资料、血清Ig、常规肿瘤标志物水平比较[（$ \bar x \pm s $）/n（%）]
Table 1. Comparison of general data，serum Ig and conventional tumor markers among the 3 groups [（$ \bar x \pm s $）/n（%）]
组别 n 性别（男/女） 年龄（岁） 体重指数（kg/m2） IgA（g/L） IgG（g/L） IgM（g/L） AFP（ng/mL） CK19（ng/mL） GP73（μg/L） 肝癌组 100 65/35 60.35±7.28 22.86±1.85 1.15±0.38ab 6.18±1.36ab 0.75±0.24ab 91.47±28.52ab 147.52±39.16ab 171.28±32.25ab 良性组 50 30/20 58.41±8.13 23.09±1.91 2.23±0.60b 8.02±1.51b 1.03±0.31b 49.65±15.41b 34.02±10.58b 91.15±21.32b 对照组 50 26/24 57.62±8.29 23.51±1.87 3.12±0.75 9.86±1.92 1.46±0.39 14.96±4.63 12.86±3.49 51.73±15.94 F/χ2 2.364 2.395 2.015 225.289 94.439 93.039 216.746 487.193 384.338 P 0.307 0.094 0.136 <0.001* <0.001* <0.001* <0.001* <0.001* <0.001* 与良性组比较，aP < 0.05；与对照组比较，bP < 0.05；*P < 0.05。 
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表 2 肝癌组血清Ig与常规肿瘤标志物水平的相关性分析
Table 2. Correlation analysis between serum Ig and the level of conventional tumor markers in liver cancer group
指标 AFP CK19 GP73 IgA r −0.465 −0.627 −0.513 P <0.001* <0.001* <0.001* IgG r −0.382 −0.516 −0.439 P 0.007* <0.001* 0.001* IgM r −0.369 −0.482 −0.405 P 0.011* <0.001* 0.004* *P < 0.05。
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表 3 不同疗效患者病情资料、血清Ig、常规肿瘤标志物水平及变化值比较[（$ \bar x \pm s $）/n（%）]（1）
Table 3. Comparison of disease data，serum Ig，conventional tumor marker levels and change values of patients with different efficacy [（$ \bar x \pm s $）/n（%）]（1）
组别 n 性别 年龄（岁） 肿瘤大小（cm） 肿瘤数量（个） 肿瘤位置 肝功能Child-Pugh分级 男 女 <60 ≥60 <5 ≥5 1 ≥2 右上腹 左上腹 A级 B级 疗效不良 32 20
（62.50）12
（37.50）21
（65.63）11
（34.38）12
（37.50）20
（62.50）10
（31.25）22
（68.75）24
（75.00）8
（25.00）15
（46.88）17
（53.13）疗效良好 68 45
（66.18）23
（33.82）35
（51.47）33
（48.53）35
（51.47）33
（48.53）33
（48.53）35
（51.47）49
（72.06）19
（27.94）43
（63.24）25
（36.76）χ2/t 0.129 1.769 1.705 2.651 0.096 2.391 P 0.719 0.184 0.192 0.104 0.757 0.122
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3 不同疗效患者病情资料、血清Ig、常规肿瘤标志物水平及变化值比较[（$ \bar x \pm s $）/n（%）]（2）
3. Comparison of disease data，serum Ig，conventional tumor marker levels and change values of patients with different efficacy [（$ \bar x \pm s $）/n（%）]（2）
IgA（g/L） IgG（g/L） IgM（g/L） 治疗前 治疗后 △ 治疗前 治疗后 △ 治疗前 治疗后 △ 0.78±0.21 1.52±0.26a 0.74±0.23 5.13±0.87 5.95±0.98a 0.82±0.27 0.56±0.18 0.76±0.21a 0.20±0.06 1.32±0.31 2.47±1.86a 1.15±0.37 6.67±1.15 8.46±1.39a 1.21±0.36 0.84±0.22 1.16±0.30a 0.32±0.10 8.925 2.869 5.758 6.718 9.186 5.444 6.274 6.792 6.268 <0.001* 0.005* <0.001* <0.001* <0.001* <0.001* <0.001* <0.001* <0.001*
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表 4 血清Ig及常规肿瘤标志物水平变化值与TACE疗效的相关性
Table 4. Correlation between serum Ig and routine tumor marker levels and TACE efficacy
指标 △IgA △IgG △IgM △AFP △CK19 △GP73 TACE疗效 r 0.462 0.437 0.518 0.405 0.379 0.391 P <0.001* 0.001* <0.001* 0.005* 0.015* 0.012* *P < 0.05。
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3 不同疗效患者病情资料、血清Ig、常规肿瘤标志物水平及变化值比较[（$ \bar x \pm s $）/n（%）]（3）
3. Comparison of disease data，serum Ig，conventional tumor marker levels and change values of patients with different efficacy [（$ \bar x \pm s $）/n（%）]（3）
AFP（ng/mL） CK19（ng/mL） GP73（μg/L） 治疗前 治疗后 △ 治疗前 治疗后 △ 治疗前 治疗后 △ 112.53±24.18 93.90±20.76a 18.63±6.14 195.27±32.39 135.09±28.14a 60.18±20.01 207.36±29.17 168.12±25.19a 39.24±12.76 81.56±25.34 53.84±16.27a 27.72±9.15 125.05±36.21 38.69±11.24a 86.36±27.54 154.30±31.46 97.26±22.04a 57.04±18.73 5.784 10.491 5.099 9.346 24.501 4.808 8.048 14.320 4.865 <0.001* <0.001* <0.001* <0.001* <0.001* <0.001* <0.001* <0.001* <0.001* 与同组治疗前比较，aP < 0.05；△表示对应指标治疗前后变化值的绝对值；*P < 0.05。
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表 5 血清Ig及常规肿瘤标志物水平变化值预测疗效的价值
Table 5. Value of serum Ig and routine tumor markers in predicting curative effect
指标 AUC 95%CI 截断值 敏感度（%） 特异度（%） P △IgA 0.777 0.682～0.854 0.90 g/L 68.75 79.41 <0.001* △IgG 0.784 0.690～0.860 1.00 g/L 90.62 60.29 <0.001* △IgM 0.793 0.701～0.868 0.25 g/L 90.62 58.82 <0.001* △AFP 0.779 0.685～0.856 21.01 ng/mL 87.50 66.18 <0.001* △CK19 0.710 0.610～0.796 69.89 ng/mL 87.50 48.53 <0.001* △GP73 0.746 0.649～0.828 45.97 μg/L 90.62 50.01 <0.001* *P < 0.05。
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表 6 含与不含Ig预测方案对疗效的预测价值比较
Table 6. Comparison of the predictive value of treatment with and without Ig
成对对比 AUC差异（95%CI，P） NRI（95%CI，P） IDI（95%CI，P） 含Ig预测方案vs不含Ig预测方案 0.111（0.007～0.215，0.036*） 0.028（0.017～0.050，0.012*） 0.046（0.35～0.063，0.024*） *P < 0.05。
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