Predictive value of serum MMP-9， FABP5 combined with MRI for the efficacy and recurrence of primary liver cancer after percutaneous radiofrequency ablation

doi:10.3760/cma.j.cn371439-20241030-00061

Abstract

Abstract:

Objective To investigate the predictive value of serum matrix metalloproteinase-9 （MMP-9）， fatty acid-binding protein 5 （FABP5） combined with MRI for the efficacy and recurrence of primary liver cancer after percutaneous radiofrequency ablation. Methods A total of 192 patients with primary liver cancer who underwent percutaneous radiofrequency ablation treatment at the First Affiliated Hospital of Air Force Medical University from June 2022 to May 2023 were selected as the research subjects. MRI examination was performed within one week before the treatment， and the apparent diffusion coefficient （ADC） value was recorded. The enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of MMP-9 and FABP5 in the serum. According to the results of MRI examination， the ablation status of the lesions was determined， and the patients were divided into a complete ablation group （n=157） and a residual lesion group （n=35）. Patients with completely ablated lesions were regularly followed up for one year， and their recurrence status was recorded. According to the recurrence of the patients， the patients were divided into a non-recurrence group （n=115） and a recurrence group （n=42）. The levels of MMP-9 and FABP5 and the ADC values of the patients in the complete ablation group and the residual lesion group， as well as those in the non-recurrence group and the recurrence group， were compared. The receiver operator characteristic （ROC） curve was used to evaluate the predictive value of serum MMP-9 and FABP5 combined with MRI for the postoperative efficacy and recurrence of the patients. Results The levels of serum MMP-9 and FABP5， and the ADC value of patients in the complete ablation group were （181.05±29.68） ng/ml，（7.95±1.82） μg/L， and （1.32±0.45）×10^-3 mm²/s， respectively， while those in the residual lesion group were （202.18±35.06） ng/ml，（9.56±2.39） μg/L， and （0.75±0.23）×10^-3 mm²/s， respectively. The levels of MMP-9 and FABP5 in the complete ablation group were significantly lower than those in the residual lesion group， and the ADC value was significantly higher than that in the residual lesion group， with statistically significant differences （t=3.68， P<0.001； t=4.45， P<0.001； t=7.27， P<0.001）. The areas under the curve （AUC） of serum MMP-9， FABP5， and ADC value alone in predicting the postoperative efficacy of patients were 0.68 （95%CI： 0.61-0.75）， 0.75 （95%CI： 0.68-0.81）， and 0.90 （95%CI： 0.85-0.94）， respectively. The AUC of the combined prediction of these three was 0.94 （95%CI： 0.89-0.97）， and the combined prediction of these three was superior to the individual prediction of MMP-9， FABP5， and ADC value （Z=5.72， P<0.001； Z=4.84， P<0.001； Z=2.29， P=0.022）. The levels of serum MMP-9 and FABP5， and the ADC value of patients in the non-recurrence group were （176.52±30.28） ng/ml，（8.69±1.92） μg/L， and （1.35±0.29）×10^-3 mm²/s， respectively， while those in the recurrence group were （201.85±28.72） ng/ml，（11.05±2.86） μg/L， and （1.14±0.12）×10^-3 mm²/s， respectively. The levels of serum MMP-9 and FABP5 of patients in the non-recurrence group were significantly lower than those in the recurrence group， and the ADC value was significantly higher than that in the recurrence group， with statistically significant differences （t=4.70， P<0.001； t=5.93， P<0.001； t=4.55， P<0.001）. The AUCs of serum MMP-9， FABP5， and ADC value alone in predicting the postoperative recurrence of patients were 0.74 （95%CI： 0.66-0.81）， 0.90 （95%CI： 0.84-0.94）， and 0.74 （95%CI： 0.66-0.80）， respectively. The AUC of the combined prediction of these three was 0.95 （95%CI： 0.90-0.98）， and the combined prediction of these three was superior to the individual prediction of MMP-9， FABP5， and ADC value （Z=5.00， P<0.001； Z=3.03， P=0.002； Z=5.33， P<0.001）. Conclusions The levels of serum MMP-9 and FABP5 in patients with primary liver cancer treated by percutaneous radiofrequency ablation in the complete ablation group are significantly lower than those in the residual lesion group， and the ADC value is significantly higher than that in the residual lesion group. The levels of serum MMP-9 and FABP5 of patients in the non-recurrence group are also significantly lower than those in the recurrence group， and the ADC value is also significantly higher than that in the recurrence group. The combined detection of serum MMP-9， FABP5 and MRI has a relatively high clinical value in predicting the efficacy and recurrence of patients after percutaneous radiofrequency ablation for liver cancer.

Key words: Liver neoplasms, Radiofrequency ablation, Matrix metalloproteinase 9, Fatty acid binding protein 5, Magnetic resonance imaging

Yang Xiaobin, Jiang Jinquan. Predictive value of serum MMP-9， FABP5 combined with MRI for the efficacy and recurrence of primary liver cancer after percutaneous radiofrequency ablation[J]. Journal of International Oncology, 2025, 52(6): 360-365.

Figures/Tables 9

References 20

[1]	Tan EY, Danpanichkul P, Yong JN, et al. Liver cancer in 2021: Global Burden of Disease study[J]. J Hepatol, 2025, 82(5): 851-860. DOI: 10.1016/j.jhep.2024.10.031.
[2]	Danpanichkul P, Suparan K, Sukphutanan B, et al. Changes in the epidemiological trends of primary liver cancer in the Asia-Pacific region[J]. Sci Rep, 2024, 14(1): 19544. DOI: 10.1038/s41598-024-70526-z.
[3]	Mejia JC, Pasko J. Primary liver cancers: intrahepatic cholangiocarcinoma and hepatocellular carcinoma[J]. Surg Clin North Am, 2020, 100(3): 535-549. DOI: 10.1016/j.suc.2020.02.013. pmid: 32402299
[4]	高欢欢, 王松太, 钱煜佳, 等. 增强CT联合增强MRI对结直肠癌患者肝转移的诊断效能[J]. 淮海医药, 2025, 43(2): 126-131. DOI: 10.14126/j.cnki.1008-7044.2025.02.004.
[5]	van den Brink H, Doubal FN, Duering M. Advanced MRI in cerebral small vessel disease[J]. Int J Stroke, 2023, 18(1): 28-35. DOI: 10.1177/17474930221091879.
[6]	Huang H. Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: recent advances[J]. Sensors (Basel), 2018, 18(10): 3249. DOI: 10.3390/s18103249.
[7]	Kim IS, Yang WS, Kim CH, et al. Physiological properties, functions, and trends in the matrix metalloproteinase inhibitors in inflammation-mediated human diseases[J]. Curr Med Chem, 2023, 30(18): 2075-2112. DOI: 10.2174/0929867329666220823112731.
[8]	George Warren W, Osborn M, Yates A, et al. The emerging role of fatty acid binding protein 5(FABP5) in cancers[J]. Drug Discov Today, 2023, 28(7): 103628. DOI: 10.1016/j.drudis.2023.103628.
[9]	Jin R, Hao J, Yu J, et al. Role of FABP5 in T cell lipid metabolism and function in the tumor microenvironment[J]. Cancers (Basel), 2023, 15(3): 657. DOI: 10.3390/cancers15030657.
[10]	中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版)[J]. 中华消化外科杂志, 2020, 19(1): 1-20. DOI: 10.3760/cma.j.issn.1673-9752.2020.01.001.
[11]	Rumgay H, Ferlay J, de Martel C, et al. Global, regional and national burden of primary liver cancer by subtype[J]. Eur J Cancer, 2022, 161: 108-118. DOI: 10.1016/j.ejca.2021.11.023.
[12]	Izzo F, Granata V, Grassi R, et al. Radiofrequency ablation and microwave ablation in liver tumors: an update[J]. Oncologist, 2019, 24(10): e990-e1005. DOI: 10.1634/theoncologist.2018-0337.
[13]	Chapiro J, Lin M, Duran R, et al. Assessing tumor response after loco-regional liver cancer therapies: the role of 3D MRI[J]. Expert Rev Anticancer Ther, 2015, 15(2): 199-205. DOI: 10.1586/14737140.2015.978861.
[14]	姚升娟, 曲静琦, 曹宇, 等. MRI联合血清miR-204水平对原发性肝癌经皮穿刺射频消融术后疗效及复发的预测价值[J]. 放射学实践, 2022, 37(1): 62-67. DOI: 10.13609/j.cnki.1000-0313.2022.01.011.
[15]	Rashid ZA, Bardaweel SK. Novel matrix metalloproteinase-9 (MMP-9) inhibitors in cancer treatment[J]. Int J Mol Sci, 2023, 24(15): 12133. DOI: 10.3390/ijms241512133.
[16]	黄文波. 血清TK1、MMP-9检测对原发性肝癌预后的评估价值[J]. 中国医师杂志, 2022, 24(5): 723-727, 732. DOI: 10.3760/cma.j.cn431274-20210309-00274.
[17]	吉婷婷, 史良玉. 射频消融联合TACE对原发性肝癌患者血清甲胎蛋白、基质金属蛋白酶-9水平的影响[J]. 临床医学研究与实践, 2023, 8(19): 80-83. DOI: 10.19347/j.cnki.2096-1413.202319020.
[18]	Xu B, Chen L, Zhan Y, et al. The biological functions and regulatory mechanisms of fatty acid binding protein 5 in various diseases[J]. Front Cell Dev Biol, 2022, 10: 857919. DOI: 10.3389/fcell.2022.857919.
[19]	覃文办, 谢一嫏, 陈金杰, 等. 血清SEMA-3B及suPAR和FABP5对中晚期肝癌患者预后评估的应用价值[J]. 中国病毒病杂志, 2022, 12(3): 214-220. DOI: 10.16505/j.2095-0136.2022.0055.
[20]	盖雪, 李国华, 付荣, 等. 多层螺旋CT灌注扫描联合血清FABP5,SEMA-3B对老年原发性肝癌的诊断和预后评估价值[J]. 中国老年学杂志, 2023, 43(15): 3639-3642. DOI: 10.3969/j.issn.1005-9202.2023.15.017.

一般资料	完全消融组（n=157）	病灶残留组（n=35）	χ²值	P值
性别
男	82（52.23）	19（54.29）	0.05	0.826
女	75（47.77）	16（45.71）	0.05	0.826
年龄（岁）
≥60	88（56.05）	20（57.14）	0.01	0.906
<60	69（43.95）	15（42.86）	0.01	0.906
高血压
有	95（60.51）	24（68.57）	0.79	0.374
无	62（39.49）	11（31.43）	0.79	0.374
糖尿病
有	86（54.78）	21（60.00）	0.32	0.574
无	71（45.22）	14（40.00）	0.32	0.574
肿瘤最大径（cm）
≤2	112（71.34）	12（34.29）	17.18	<0.001
>2	45（28.66）	23（65.71）	17.18	<0.001
淋巴结转移
有	59（37.58）	20（57.14）	4.52	0.033
无	98（62.42）	15（42.86）	4.52	0.033
Child-Pugh分级
A级	116（73.89）	16（45.71）	10.57	0.001
B级	41（26.11）	19（54.29）	10.57	0.001

变量	截断值	AUC	95%CI	敏感性（%）	特异性（%）	Youden 指数
MMP-9	188.78 ng/ml	0.68	0.61~0.75	68.57	62.42	0.31
FABP5	9.74 μg/L	0.75	0.68~0.81	66.24	71.42	0.38
ADC值	0.93×10^-3 mm²/s	0.90	0.85~0.94	94.29	80.25	0.75
三者联合	-	0.94	0.89~0.97	94.29	83.44	0.78

一般资料	未复发组（n=115）	复发组（n=42）	χ²值	P值
性别
男	60（52.17）	22（52.38）	<0.01	0.982
女	55（47.83）	20（47.62）	<0.01	0.982
年龄（岁）
≥60	62（53.91）	26（61.90）	0.80	0.372
<60	53（46.09）	16（38.10）	0.80	0.372
高血压
有	67（58.26）	28（66.67）	0.91	0.340
无	48（41.74）	14（33.33）	0.91	0.340
糖尿病
有	60（52.17）	26（61.90）	1.18	0.278
无	55（47.83）	16（38.10）	1.18	0.278
肿瘤最大径（cm）
≤2	97（84.35）	12（28.57）	45.09	<0.001
>2	18（15.65）	30（71.43）	45.09	<0.001
淋巴结转移
有	34（29.57）	25（59.52）	11.77	0.001
无	81（70.43）	17（40.48）	11.77	0.001
Child-Pugh分级
A级	102（88.70）	14（33.33）	48.87	<0.001
B级	13（11.30）	28（66.67）	48.87	<0.001

变量	截断值	AUC	95%CI	敏感性（%）	特异性（%）	Youden 指数
MMP-9	186.20 ng/ml	0.74	0.66~0.81	73.81	68.70	0.43
FABP5	9.91 μg/L	0.90	0.84~0.94	73.81	93.04	0.67
ADC值	1.2×10^-3 mm²/s	0.74	0.66~0.80	88.10	57.39	0.46
三者联合	-	0.95	0.90~0.98	80.95	96.52	0.78