超声造影联合血清CXCL8、CXCR2在原发性肝癌经导管动脉化疗栓塞术后疗效评估中的价值分析

摘要/Abstract

摘要：

目的探讨超声造影联合血清CXC趋化因子配体8（CXCL8）、CXC趋化因子受体2（CXCR2）水平检测在原发性肝癌患者经导管动脉化疗栓塞术（TACE）治疗后疗效评估中的应用价值。方法选取2019年6月至2022年1月湖北省黄冈市中心医院诊治的80例原发性肝癌患者为研究对象，TACE治疗2个月后评估治疗疗效，根据病理诊断结果分为完全灭活组（n=30）和病灶残留组（n=50）。采用酶联免疫吸附双抗体夹心法检测患者血清CXCL8、CXCR2水平，并对患者进行超声造影检查；采用受试者工作特征（ROC）曲线分析血清CXCL8、CXCR2评估原发性肝癌患者TACE治疗后疗效的价值；超声造影及超声造影联合血清CXCL8、CXCR2评估原发性肝癌患者TACE治疗后疗效与病理诊断结果的一致性采用Kappa检验。结果与完全灭活组比较，病灶残留组血清CXCL8[（7.12±1.68）ng/mlvs. （5.07±1.25）ng/ml]、CXCR2[（3.62±0.79）ng/mlvs. （2.43±0.67）ng/ml]水平均较高（t=5.79，P<0.001；t=6.89，P<0.001）。CXCL8、CXCR2评估原发性肝癌患者TACE治疗后疗效的曲线下面积分别为0.827、0.801，特异性分别为73.3%、76.7%，敏感性分别为70.0%、72.0%。超声造影评估原发性肝癌患者TACE治疗后疗效与病理诊断结果一致性为中度，Kappa值为0.49（P<0.001）。超声造影联合血清CXCL8、CXCR2评估原发性肝癌患者TACE治疗后疗效与病理诊断结果一致性为较高，Kappa值为0.62（P<0.001）。超声造影联合血清CXCL8、CXCR2评估原发性肝癌患者TACE治疗后疗效的敏感性为90.0%，高于超声造影（72.0%，χ²=5.26，P=0.022）、CXCL8（70.0%，χ²=6.25，P=0.012）和CXCR2（72.0%，χ²=5.26，P=0.022）单独评估。结论超声造影可一定程度检出原发性肝癌患者TACE治疗后的病灶残留，且其联合血清CXCL8、CXCR2可有效提高原发性肝癌患者TACE治疗后疗效的评估效能。

关键词:肝肿瘤,超声检查,造影剂,经导管动脉化疗栓塞术

Abstract:

ObjectiveTo investigate the application value of contrast-enhanced ultrasound combined with serum CXC chemokine ligand 8 （CXCL8） and CXC chemokine receptor 2 （CXCR2） levels detection in the efficacy evaluation of patients with primary liver cancer after transcatheter arterial chemoembolization （TACE）.MethodsA total of 80 patients with primary liver cancer who were diagnosed and treated in Huanggang Central Hospital of Hubei Province from June 2019 to January 2022 were selected as the research objects. The therapeutic efficacy was evaluated 2 months after TACE treatment. According to the pathological diagnosis， the patients were divided into complete inactivation group （n=30） and residual lesion group （n=50）. The levels of serum CXCL8 and CXCR2 were measured by enzyme linked immunosorbent assay （ELISA） double antibody sandwich method， and contrast-enhanced ultrasonography was performed on the patients. Receiver operating characteristic （ROC） curve was applied to analyze the value of serum CXCL8 and CXCR2 in evaluating the efficacy of TACE in patients with primary liver cancer. Kappa test was applied to test the consistency of contrast-enhanced ultrasound and contrast-enhanced ultrasound combined with serum CXCL8 and CXCR2 in evaluating the efficacy of TACE in patients with primary liver cancer and the results of pathological diagnosis.ResultsCompared with the complete inactivation group， the levels of serum CXCL8 [（7.12±1.68） ng/mlvs. （5.07±1.25） ng/ml] and CXCR2 [（3.62±0.79） ng/mlvs.（2.43±0.67） ng/ml] in the residual lesion group were obviously higher （t=5.79，P<0.001；t=6.89，P<0.001）. The areas under the curve of CXCL8 and CXCR2 in evaluating the efficacy of TACE in patients with primary liver cancer were 0.827 and 0.801 respectively， the specificities were 73.3% and 76.7%， and the sensitivities were 70.0% and 72.0% respectively. The concordance between contrast-enhanced ultrasound and pathological diagnosis was moderate， and the Kappa value was 0.49 （P<0.001）. The concordance between contrast-enhanced ultrasound combined with serum CXCL8 and CXCR2 and pathological diagnosis was high， and the Kappa value was 0.62 （P<0.001）. The sensitivity of contrast-enhanced ultrasound combined with serum CXCL8 and CXCR2 in evaluating the efficacy of TACE in patients with primary liver cancer was 90.0%， which was higher than the sensitivity of contrast-enhanced ultrasound （72.0%，χ²=5.26，P=0.022）， CXCL8 （70.0%，χ²=6.25，P=0.012） and CXCR2 （72.0%，χ²=5.26，P=0.022）.ConclusionContrast-enhanced ultrasound can detect residual lesions after TACE in patients with primary liver cancer to a certain extent， and its combination with serum CXCL8 and CXCR2 can effectively improve the evaluation efficiency of the efficacy of TACE treatment in patients with primary liver cancer.

Key words:Liver neoplasms,Ultrasonography,Contrast media,Transcatheter arterial chemoembolization

张玉敏, 赵现伟, 何前进, 陈杰能. 超声造影联合血清CXCL8、CXCR2在原发性肝癌经导管动脉化疗栓塞术后疗效评估中的价值分析[J]. 国际肿瘤学杂志, 2022, 49(10): 592-596.

Zhang Yumin, Zhao Xianwei, He Qianjin, Chen Jieneng. Value of contrast-enhanced ultrasound combined with serum CXCL8 and CXCR2 in the evaluation of postoperative efficacy of transcatheter arterial chemoembolization for primary liver cancer[J]. Journal of International Oncology, 2022, 49(10): 592-596.

图/表7

组别	CXCL8	CXCR2
完全灭活组（n=30）	5.07±1.25	2.43±0.67
病灶残留组（n=50）	7.12±1.68	3.62±0.79
t值	5.79	6.89
P值	<0.001	<0.001

表1

图1

图2

图3

超声造影	病理诊断	Kappa值	P值
阳性	36	6	0.49	<0.001
阴性	14	24

表2

超声造影联合血清 CXCL8、CXCR2	病理学诊断	Kappa值	P值
阳性	45	9	0.62	<0.001
阴性	5	21

表3

表4

超声造影、血清CXCL8、CXCR2及三者联合对80例原发性肝癌患者TACE治疗后疗效的评估效能比较（%）"

评估效能	超声造影	CXCL8	CXCR2	三者联合	超声造影vs.三者联合		CXCL8vs.三者联合		CXCR2vs.三者联合
评估效能	超声造影	CXCL8	CXCR2	三者联合	χ²值	P值	χ²值	P值	χ²值	P值
敏感性	72.0	70.0	72.0	90.0	5.26	0.022	6.25	0.012	5.26	0.022
特异性	80.0	73.3	76.7	70.0	0.80	0.371	0.08	0.774	0.34	0.559
阳性预测值	85.7	81.4	83.7	83.3	0.10	0.750	0.06	0.803	<0.01	0.959
阴性预测值	63.2	59.5	62.2	80.8	2.29	0.130	3.20	0.074	2.51	0.113
准确率	75.0	71.3	73.8	82.5	1.35	0.246	2.85	0.092	1.79	0.181

表4

参考文献17

[1]	Philips CA, Rajesh S, Nair DC, et al. Hepatocellular carcinoma in 2021: an exhaustive update[J]. Cureus, 2021, 13(11): e19274. DOI: 10.7759/cureus.19274. doi:10.7759/cureus.19274
[2]	Zhu C, Chen H, Fang Q, et al. Improvement in the condition of patients with primary liver cancer with transcatheter arterial chemoembolization before and after microwave ablation interventional therapy[J]. Am J Transl Res, 2021, 13(10): 11908-11916. pmid:34786121
[3]	Fu Z, Li X, Zhong J, et al. Lenvatinib in combination with transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma (uHCC): a retrospective controlled study[J]. Hepatol Int, 2021, 15(3): 663-675. DOI: 10.1007/s12072-021-10184-9. doi:10.1007/s12072-021-10184-9pmid:33877527
[4]	Dong Y, Wang WP, Mao F, et al. Imaging features of fibrolamellar hepatocellular carcinoma with contrast-enhanced ultrasound[J]. Ultraschall Med, 2021, 42(3): 306-313. DOI: 10.1055/a-1110-7124. doi:10.1055/a-1110-7124
[5]	中国医师协会放射肿瘤治疗医师分会, 中华医学会放射肿瘤治疗学分会, 中国抗癌协会肿瘤放射治疗专业委员会. 中国原发性肝细胞癌放射治疗指南(2020年版)[J]. 国际肿瘤学杂志, 2021, 48(1): 1-10. DOI: 10.3760/cma.j.cn371439-20201208-00001. doi:10.3760/cma.j.cn371439-20201208-00001
[6]	Ghanaati H, Mohammadifard M, Mohammadifard M. A review of applying transarterial chemoembolization (TACE) method for management of hepatocellular carcinoma[J]. J Family Med Prim Care, 2021, 10(10): 3553-3560. DOI: 10.4103/jfmpc.jfmpc_2347_20. doi:10.4103/jfmpc.jfmpc_2347_20pmid:34934646
[7]	Jeong J, Park JG, Seo KI, et al. Microvascular invasion may be the determining factor in selecting TACE as the initial treatment in patients with hepatocellular carcinoma[J]. Medicine (Baltimore), 2021, 100(27): e26584. DOI: 10.1097/MD.0000000000026584. doi:10.1097/MD.0000000000026584
[8]	Shao L, Wang X, Yu Y, et al. Comparative analysis of the efficacy and accuracy of magnetic resonance imaging (MRI) and contrast-enhanced CT for residual and new lesions after transcatheter arterial chemoembolization (TACE) in patients with primary liver cancer[J]. Transl Cancer Res, 2021, 10(8): 3739-3747. DOI: 10.21037/tcr-21-831. doi:10.21037/tcr-21-831pmid:35116674
[9]	Yue X, Jiang Q, Hu X, et al. Quantitative dual-energy CT for eva-luating hepatocellular carcinoma after transarterial chemoembolization[J]. Sci Rep, 2021, 11(1): 11127. DOI: 10.1038/s41598-021-90508-9. doi:10.1038/s41598-021-90508-9
[10]	Yang S, Wang H, Qin C, et al. Up-regulation of CXCL8 expression is associated with a poor prognosis and enhances tumor cell malignant behaviors in liver cancer[J]. Biosci Rep, 2020, 40(8): BSR20201169. DOI: 10.1042/BSR20201169. doi:10.1042/BSR20201169
[11]	Wan Y, Ge K, Zhou W, et al. C-X-C chemokine receptor 2 (Cxcr2) promotes hepatocellular carcinoma immune evasion via regulating programmed death-ligand 1 (PD-L1)[J]. Biol Chem, 2021, 402(6): 729-737. DOI: 10.1515/hsz-2020-0328. doi:10.1515/hsz-2020-0328pmid:33583159
[12]	孔健, 张文轩, 孙文兵. 肿瘤内皮来源CXC趋化因子配体8对肝细胞癌血管生成拟态的影响[J]. 中华实验外科杂志, 2020, 37(12): 2229-2231. DOI: 10.3760/cma.j.cn421213-20200820-00623. doi:10.3760/cma.j.cn421213-20200820-00623
[13]	Hakobyan K, Gaddam M, Ojinnaka U, et al. Contrast-enhanced ultrasound as a main radiological diagnostic method for primary liver neoplasms and hemangiomas[J]. Cureus, 2021, 13(9): e18288. DOI: 10.7759/cureus.18288. doi:10.7759/cureus.18288
[14]	Hai Y, Savsani E, Chong W, et al. Meta-analysis and systematic review of contrast-enhanced ultrasound in evaluating the treatment response after locoregional therapy of hepatocellular carcinoma[J]. Abdom Radiol (NY), 2021, 46(11): 5162-5179. DOI: 10.1007/s00261-021-03248-9. doi:10.1007/s00261-021-03248-9pmid:34410432
[15]	张心荣, 欧阳骏, 黄敬垣. CEUS和增强CT对原发性肝癌TACE术后疗效的评估价值比较[J]. 世界华人消化杂志, 2019, 27(1): 63-67. DOI: 10.11569/wcjd.v27.i1.63. doi:10.11569/wcjd.v27.i1.63
[16]	Fraquelli M, Nadarevic T, Colli A, et al. Contrast-enhanced ultrasound for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease[J]. Cochrane Database Syst Rev, 2022, 9(9): CD013483. DOI: 10.1002/14651858.CD013483.pub2. doi:10.1002/14651858.CD013483.pub2
[17]	李丛辉, 罗红缨, 王建钧, 等. 超声造影联合血γ-GT水平在原发性肝癌患者TACE术后疗效评估中的价值[J]. 肝脏, 2021, 26(3): 266-269. DOI: 10.3969/j.issn.1008-1704.2021.03.014. doi:10.3969/j.issn.1008-1704.2021.03.014