NLR、TNF-α水平对巨块型肝癌患者TACE联合微波消融治疗效果的预测分析

摘要/Abstract

摘要：

目的探讨中性粒细胞与淋巴细胞比值（NLR）、肿瘤坏死因子-α（TNF-α）水平对巨块型肝癌患者经动脉化疗栓塞术（TACE）联合微波消融治疗效果的预测价值。方法回顾性分析2020年2月—2023年2月潍坊医学院附属医院行TACE联合微波消融治疗的106例巨块型肝癌患者病历资料，术后6周评估疗效，根据治疗效果将患者分为缓解组、未缓解组。分别于术前、术后3 d和术后7 d检测两组NLR、TNF-α水平，采用点二列相关性分析不同时间段NLR、TNF-α水平与巨块型肝癌患者TACE联合微波消融治疗效果的关系，绘制受试者操作特征（ROC）曲线分析不同时间段NLR、TNF-α水平对巨块型肝癌患者TACE联合微波消融治疗效果的预测价值。结果术后6周，106例巨块型肝癌患者中完全缓解13例，部分缓解48例，疾病进展20例，病情稳定25例，总缓解率为57.55%（61/106）。术前，缓解组（n=61）NLR[（2.26±0.13）比（2.43±0.12），t=6.87，P<0.001]、TNF-α水平[（36.20±4.38）pg/ml比（42.74±5.74）pg/ml，t=6.66，P<0.001]均低于未缓解组（n=45），差异有统计学意义；术后3 d，缓解组与未缓解组NLR[（6.16±3.22）比（6.22±3.30），t=0.09，P=0.925]、TNF-α水平[（48.84±7.22）pg/ml比（49.13±7.34）pg/ml，t=0.20，P=0.840]比较，差异均无统计学意义；术后7 d，缓解组NLR[（2.60±0.18）比（2.82±0.26），t=5.15，P<0.001]、TNF-α水平[（38.20±6.30）pg/ml比（45.57±5.79）pg/ml，t=6.16，P<0.001]均低于未缓解组，差异均有统计学意义。缓解组与未缓解组术前、术后3 d、术后7 d的NLR、TNF-α水平差异均有统计学意义（F=82.43，P<0.001；F=54.45，P<0.001；F=76.23，P<0.001；F=15.61，P<0.001）。进一步两两比较发现，与术前相比，两组术后3 d、术后7 d的NLR、TNF-α水平均更高，但两组术后7 d NLR、TNF-α水平均低于术后3 d，差异均有统计学意义（均P<0.05）。点二列相关性分析显示，术前及术后7 d NLR、TNF-α水平与巨块型肝癌患者TACE联合微波消融治疗效果均呈现出显著正相关（r=0.42，P<0.001；r=0.49，P<0.001；r=0.43，P<0.001；r=0.46，P<0.001）。ROC曲线分析显示，术前及术后7 d NLR、TNF-α水平单独预测巨块型肝癌患者TACE联合微波消融治疗效果的曲线下面积（AUC）分别为0.750（95%CI为0.656~0.844）、0.788（95%CI为0.699~0.877）、0.751（95%CI为0.652~0.850）、0.788（95%CI为0.700~0.876），术前及术后7 d NLR、TNF-α水平联合预测的AUC分别为0.818（95%CI为0.736~0.900）、0.813（95%CI为0.730~0.897）。术前及术后7 d NLR、TNF-α水平单独及联合预测巨块型肝癌患者TACE联合微波消融治疗效果的AUC比较，差异均无统计学意义（均P>0.05）。结论术前及术后7 d时NLR、TNF-α水平均与巨块型肝癌患者TACE联合微波消融治疗效果有关，且术前及术后7 d NLR、TNF-α水平联合检测对巨块型肝癌患者TACE联合微波消融治疗效果均具有一定的预测效能。

关键词:肝肿瘤,中性粒细胞与淋巴细胞比值,肿瘤坏死因子α,经动脉化疗栓塞术,微波消融

Abstract:

ObjectiveTo explore the predictive value of neutrophil-to-lymphocyte ratio （NLR） and tumor necrosis factor -α （TNF-α） level on the therapeutic effect of transcatheter arterial chemoembolization （TACE） combined with microwave ablation in patients with massive liver cancer.MethodsThe medical records of 106 patients with massive liver cancer who underwent TACE combined with microwave ablation treatment in the Affiliated Hospital of Weifang Medical University from February 2020 to February 2023 were retrospectively analyzed. The efficacy was evaluated 6 weeks after surgery， and the patients were divided into remission group and non-remission group according to the therapeutic effect. The levels of NLR and TNF-α in the two groups were detected before surgery， 3 days after surgery and 7 days after surgery. Point two column correlation was used to analyze the relationship between the levels of NLR and TNF-α in different time periods and the therapeutic effect of TACE combined with microwave ablation in patients with massive liver cancer. The receiver operator characteristic （ROC） curve was drawn to analyze the predictive value of NLR and TNF-α levels in different time periods for the therapeutic effect of TACE combined with microwave ablation in patients with massive liver cancer.ResultsSix weeks after surgery， out of 106 patients with massive liver cancer， 13 achieved complete remission， 48 achieved partial remission， 20 experienced disease progression， and 25 remained stable. The overall remission rate was 57.55% （61/106）. Before surgery， the levels of NLR [（2.26±0.13）vs.（2.43±0.12），t=6.87，P<0.001] and TNF-α [（36.20±4.38） pg/mlvs.（42.74±5.74） pg/ml，t=6.66，P<0.001] in the remission group （n=61） were lower than those in the non-remission group （n=45）， with statistically significant differences. At 3 days after surgery， there were no statistically significant difference in the levels of NLR [（6.16±3.22）vs.（6.22±3.30），t=0.09，P=0.925] or TNF-α [（48.84±7.22） pg/mlvs.（49.13±7.34） pg/ml，t=0.20，P=0.840] between the remission group and the non-remission group. At 7 days after surgery， the levels of NLR [（2.60±0.18）vs.（2.82±0.26），t=5.15，P<0.001] and TNF-α [（38.20±6.30） pg/mlvs.（45.57±5.79） pg/ml，t=6.16，P<0.001] in the remission group were lower than those in the non-remission group， with statistically significant differences. There were statistically significant differences in NLR and TNF-α levels before surgery， 3 days and 7 days after surgery between the remission group and the non-remission group （F=82.43，P<0.001；F=54.45，P<0.001；F=76.23，P<0.001；F=15.61，P<0.001）. Further pair-to-pair comparison showed that the levels of NLR and TNF-α were higher in both groups 3 and 7 days after surgery than before surgery， but the levels of NLR and TNF-α were lower in both groups 7 days after surgery than 3 days after surgery， with statistically significant differences （allP<0.005）. Point two column correlation analysis showed that NLR level， TNF-α level and the efficacy of TACE combined with microwave ablation in patients with massive liver cancer were significantly positively correlated before and 7 days after surgery （r=0.42，P<0.001；r=0.49，P<0.001；r=0.43，P<0.001；r=0.46，P<0.001）. ROC curve showed that the area under the curve （AUC） of NLR and TNF-α alone in predicting the efficacy of TACE combined with microwave ablation in patients with massive liver cancer before and 7 days after surgery was 0.750 （95%CI： 0.656-0.844）， 0.788 （95%CI： 0.699-0.877）， 0.751 （95%CI： 0.652-0.850）， 0.788 （95%CI： 0.700-0.876）， respectively. The AUC of combined prediction of NLR and TNF-α before and 7 days after surgery were 0.818 （95%CI： 0.736-0.900） and 0.813 （95%CI： 0.730-0.897）， respectively. There were no statistically significant differences in the AUC values of NLR and TNF-α alone or in combination for predicting the therapeutic effect of TACE combined with microwave ablation in patients with massive liver cancer before and 7 days after surgery （allP>0.05）.ConclusionsThe levels of NLR and TNF-α before and 7 days after surgery are related to the effect of TACE combined with microwave ablation in patients with massive liver cancer， and the combination of NLR and TNF-α levels before and 7 days after surgery has certain value in predicting the effect of TACE combined with microwave ablation in patients with massive liver cancer.

Key words:Liver neoplasms,Neutrophil-to-lymphocyte ratio,Tumor necrosis factor-alpha,Transcatheter arterial chemoembolization,Microwave ablation

邢辉, 谭莹, 王秀珍, 李瑞, 刘霞. NLR、TNF-α水平对巨块型肝癌患者TACE联合微波消融治疗效果的预测分析[J]. 国际肿瘤学杂志, 2025, 52(2): 101-106.

Xing Hui, Tan Ying, Wang Xiuzhen, Li Rui, Liu Xia. Predictive analysis of NLR and TNF-α level for the efficacy of TACE combined with microwave ablation therapy in patients with massive liver cancer[J]. Journal of International Oncology, 2025, 52(2): 101-106.

图/表5

表1

两组巨块型肝癌患者基线特征比较[例（%）/ $\bar{x}±s$]"

基线资料	缓解组（n=61）	未缓解组（n=45）	χ²/t值	P值
性别
男	42（68.85）	30（66.67）	0.06	0.812
女	19（31.15）	15（33.33）	0.06	0.812
年龄（岁）	52.68±5.24	53.08±5.13	0.39	0.696
肿瘤最大径（cm）	7.02±1.18	6.96±1.24	0.25	0.801
体质量指数（kg/m²）	23.02±2.34	22.85±2.16	0.38	0.703
Child-Pugh分级
A级	16（26.23）	13（28.89）	0.09	0.761
B级	45（73.77）	32（71.11）	0.09	0.761
BCLC分期
B期	20（32.79）	16（35.56）	0.09	0.766
C期	41（67.21）	29（64.44）	0.09	0.766
肿瘤数目
单发	52（85.25）	38（84.44）	0.01	0.909
多发	9（14.75）	7（15.56）	0.01	0.909
基础病因
乙型病毒性肝炎	43（70.49）	32（71.11）	0.01	0.945
丙型病毒性肝炎	18（29.51）	13（28.89）	0.01	0.945
白蛋白（g/L）	32.85±4.12	34.08±4.20	1.51	0.135
总胆红素（μmol/L）	15.90±5.68	15.24±5.92	0.58	0.563
ALT（U/L）	56.73±15.02	58.06±15.27	0.45	0.655
AST（U/L）	72.82±11.34	70.68±10.58	0.99	0.326
甲胎蛋白（μg/L）	435.46±42.33	430.89±46.02	0.53	0.598

表1

表2

两组巨块型肝癌患者不同时间段NLR、TNF-α水平变化（$\bar{x}±s$）"

时间	NLR				TNF-α（pg/ml）
时间	缓解组（n=61）	未缓解组（n=45）	t值	P值	缓解组（n=61）	未缓解组（n=45）	t值	P值
术前	2.26±0.13	2.43±0.12	6.87	<0.001	36.20±4.38	42.74±5.74	6.66	<0.001
术后3 d	6.16±3.22^a	6.22±3.30^a	0.09	0.925	48.84±7.22^a	49.13±7.34^a	0.20	0.840
术后7 d	2.60±0.18^ab	2.82±0.26^ab	5.15	<0.001	38.20±6.30^ab	45.57±5.79^ab	6.16	<0.001
F值	82.43	54.45			76.23	15.61
P值	<0.001	<0.001			<0.001	<0.001

表2

指标	r值	P值
术前
NLR	0.42	<0.001
TNF-α	0.49	<0.001
术后7 d
NLR	0.43	<0.001
TNF-α	0.46	<0.001

表3

表4

术前及术后7 d NLR、TNF-α水平对106例巨块型肝癌患者TACE联合微波消融治疗效果的预测价值"

指标	AUC	95%CI	SE值	P值	最佳阈值	特异性	敏感性	约登指数
术前
NLR	0.750	0.656~0.844	0.048	<0.001	2.325	0.705	0.711	0.416
TNF-α	0.788	0.699~0.877	0.045	<0.001	37.945 pg/ml	0.623	0.800	0.423
联合	0.818	0.736~0.900	0.042	<0.001		0.721	0.778	0.499
术后7 d
NLR	0.751	0.652~0.850	0.051	<0.001	2.735	0.623	0.844	0.467
TNF-α	0.788	0.700~0.876	0.045	<0.001	40.210 pg/ml	0.787	0.689	0.476
联合	0.813	0.730~0.897	0.043	<0.001		0.738	0.778	0.513

表4

图1

参考文献25

[1]	Chen J, Xia C, Duan T, et al. Macrotrabecular-massive hepatocellular carcinoma: imaging identification and prediction based on gadoxetic acid-enhanced magnetic resonance imaging[J].Eur Radiol,2021,31(10): 7696-7704. DOI:10.1007/s00330-021-07898-7. pmid:33856520
[2]	张玉敏, 赵现伟, 何前进, 等. 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. DOI:10.3760/cma.j.cn371439-20220429-00117.
[3]	Liu F, Hou B, Li Z, et al. Microwave ablation of multifocal primary liver cancer guided by real-time 3.0T MRI[J].Int J Hyperthermia,2023,40(1): 2228519. DOI:10.1080/02656736.2023.2228519.
[4]	Asano K, Kageyama K, Yamamoto A, et al. Transcatheter arterial chemoembolization for treatment-naive hepatocellular carcinoma has different treatment effects depending on central or peripheral tumor location[J].Liver Cancer,2023,12(6): 576-589. DOI:10.1159/000530441. pmid:38058422
[5]	Herkel J, Schmidt-Arras D. Mediators of liver inflammation and carcinogenesis[J].Semin Immunopathol,2021,43(4): 477-479. DOI:10.1007/s00281-021-00880-x. pmid:34528106
[6]	Wu YL, Fulgenzi CAM, D'Alessio A, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as prognostic biomarkers in unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab[J].Cancers (Basel),2022,14(23): 5834. DOI:10.3390/cancers14235834.
[7]	Tiegs G, Horst AK. TNF in the liver: targeting a central player in inflammation[J].Semin Immunopathol,2022,44(4): 445-459. DOI:10.1007/s00281-022-00910-2. pmid:35122118
[8]	中华人民共和国卫生和计划生育委员会医政医管局. 原发性肝癌诊疗规范(2017年版)[J].中华肝脏病杂志,2017,25(12): 886-895. DOI:10.3760/cma.j.issn.1007-3418.2017.12.002.
[9]	Naghashzadeh F, Noorali S, Hosseini-Baharanchi FS, et al. Comparison of scores for child-pugh criteria and standard and modified models for end-stage liver disease to assess cardiac hepatopathy in heart transplant recipients[J].Exp Clin Transplant,2021,19(9): 963-969. DOI:10.6002/ect.2020.0559. pmid:34545779
[10]	Sato Y, Watanabe H, Sone M, et al. Tumor response evaluation criteria for HCC (hepatocellular carcinoma) treated using TACE (transcatheter arterial chemoembolization): RECIST (response evaluation criteria in solid tumors) version 1.1 and mRECIST (modified RECIST): JIVROSG-0602[J].Ups J Med Sci,2013,118(1): 16-22. DOI:10.3109/03009734.2012.729104.
[11]	中华人民共和国国家卫生健康委员会. 原发性肝癌诊疗指南(2022年版)[J].肿瘤防治研究,2022,49(3): 251-276. DOI:10.3971/j.issn.1000-8578.2022.03.0001.
[12]	Xie DY, Zhu K, Ren ZG, et al. A review of 2022 Chinese clinical guidelines on the management of hepatocellular carcinoma: updates and insights[J].Hepatobiliary Surg Nutr,2023,12(2): 216-228. DOI:10.21037/hbsn-22-469.
[13]	赵剑强, 朱青峰, 刘晓, 等. 基于三维可视化技术对巨块型肝癌肝动脉血管分布规律的分析与研究[J].中国医学物理学杂志,2021,38(1): 40-46. DOI:10.3969/j.issn.1005-202X.2021.01.007.
[14]	Spiliotis AE, Gäbelein G, Holländer S, et al. Microwave ablation compared with radiofrequency ablation for the treatment of liver cancer: a systematic review and meta-analysis[J].Radiol Oncol,2021,55(3): 247-258. DOI:10.2478/raon-2021-0030. pmid:34167181
[15]	Wang X, Li M, Wang J, et al. The effect of nano-albumin paclitaxel on the early postoperative recurrence of primary liver cancer[J].J Nanosci Nanotechnol,2020,20(12): 7283-7288. DOI:10.1166/jnn.2020.18710. pmid:32711592
[16]	宋佳, 胡钦勇. TACE联合靶向、免疫治疗在BCLC B/C期肝细胞癌中的应用[J].国际肿瘤学杂志,2022,49(9): 550-554. DOI:10.3760/cma.j.cn371439-20220520-00107.
[17]	Yang YM, Kim SY, Seki E. Inflammation and liver cancer: molecular mechanisms and therapeutic targets[J].Semin Liver Dis,2019,39(1): 26-42. DOI:10.1055/s-0038-1676806. pmid:30809789
[18]	Cupp MA, Cariolou M, Tzoulaki I, et al. Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies[J].BMC Med,2020,18(1): 360. DOI:10.1186/s12916-020-01817-1. pmid:33213430
[19]	Li CH, Palanisamy K, Li X, et al. Exosomal tumor necrosis factor-α from hepatocellular cancer cells (Huh-7) promote osteoclast differentiation[J].J Cell Biochem,2021,122(11): 1749-1760. DOI:10.1002/jcb.30127.
[20]	Geh D, Leslie J, Rumney R, et al. Neutrophils as potential therapeutic targets in hepatocellular carcinoma[J].Nat Rev Gastroenterol Hepatol,2022,19(4): 257-273. DOI:10.1038/s41575-021-00568-5. pmid:35022608
[21]	Minici R, Siciliano MA, Ammendola M, et al. Prognostic role of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-C reactive protein ratio (LCR) in patients with hepatocellular carcinoma (HCC) undergoing chemoembolizations (TACE) of the liver: the unexplored corner linking tumor microenvironment, biomarkers and interventional radiology[J].Cancers (Basel),2022,15(1): 257. DOI:10.3390/cancers15010257.
[22]	Heinrich B, Gertz EM, Schäffer AA, et al. The tumour micro-environment shapes innate lymphoid cells in patients with hepatocellular carcinoma[J].Gut,2022,71(6): 1161-1175. DOI:10.1136/gutjnl-2021-325288.
[23]	Zong C, Meng Y, Ye F, et al. AIF1⁺CSF1R⁺MSCs, induced by TNF-α, act to generate an inflammatory microenvironment and promote hepatocarcinogenesis[J].Hepatology,2023,78(2): 434-451. DOI:10.1002/hep.32738.
[24]	Wungu CDK, Riyanto FC, Prabowo GI, et al. Association between five types of tumor necrosis factor-α gene polymorphism and hepatocellular carcinoma risk: a meta-analysis[J].BMC Cancer,2020,20(1): 1134. DOI:10.1186/s12885-020-07606-6. pmid:33228594
[25]	朱倩, 卢贵余, 桂芬芳, 等. TNF-α对肝癌细胞NF-κB信号通路活化的影响及临床意义[J].河北医药,2018,40(24): 3700-3703. DOI:10.3969/j.issn.1002-7386.2018.24.004.