外周血细胞因子在原发性肝癌TACE术后疗效评估中的研究进展

王林; 杨小莉; 晏玉玲

doi:10.16766/j.cnki.issn.1674-4152.003741

外周血细胞因子在原发性肝癌TACE术后疗效评估中的研究进展

doi: 10.16766/j.cnki.issn.1674-4152.003741

四川大学华西医院消化内科，四川成都 610041

基金项目:

四川省自然科学基金项目 2022YFS03589

详细信息

通讯作者:
杨小莉，E-mail：xhkyxl@163.com

中图分类号: R735.7 R730.5
计量
- 文章访问数: 26
- HTML全文浏览量: 15
- PDF下载量: 1
- 被引次数: 0
出版历程
- 收稿日期: 2024-02-20
- 网络出版日期: 2024-12-31

Progress in research on peripheral blood cytokines for evaluating efficacy after TACE in primary liver cancer

Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China

摘要

摘要: 原发性肝癌是全球范围内发病率、致死率较高的恶性肿瘤之一，及时有效的治疗及精准的疗效评估对于提高患者生存率具有重要意义。经动脉化疗栓塞(TACE)是目前治疗中晚期原发性肝癌的重要方法，其疗效评估的准确性直接影响治疗策略的调整和优化。然而，目前常规的疗效评估方法，如影像学检查和临床表现评估，存在时效性差和敏感性低的局限。近年来，外周血细胞因子在TACE术后的疗效评估中展现出了一定的应用前景。本文详细探讨炎症因子如白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)，免疫调节因子如程序性细胞死亡受体-1(PD-1)，血管生成因子如血管内皮生长因子(VEGF)以及细胞生长和分化因子在TACE术后疗效评估中的作用与研究进展。这些因子的水平变化不仅能够作为肿瘤生物学行为和治疗反应的早期标志物，同时还可揭示患者的预后信息。此外，综合分析这些生物标志物的变化可为揭示肿瘤微环境的复杂性和动态变化提供更多信息，增强对肝癌治疗机制的理解。未来需要更加深入地研究这些生物标志物在TACE治疗前后的定量变化、相互作用及其与肿瘤微环境的关系，以期构建一个综合、多层面的疗效评估模型，以更精确地监控疗效，为临床提供决策支持，从而定制个性化的治疗方案，优化治疗结果，最终提高患者的生存率和生活质量。
- 原发性肝癌 /
- 经动脉化疗栓塞 /
- 外周血细胞因子 /
- 疗效评估 /
- 研究进展
Abstract: Primary liver cancer ranks among the most prevalent and deadly malignancies globally, making timely and effective treatment, along with precise efficacy assessment, crucial for improving patient survival rates. Transarterial chemoembolization (TACE) is a vital treatment for intermediate and advanced stages of primary liver cancer, and the accuracy of its efficacy assessment directly influences the adjustment and optimization of treatment strategies. However, current conventional assessment methods, such as imaging studies and clinical evaluations, face limitations in terms of timeliness and sensitivity. In recent years, peripheral blood cytokines have emerged as promising indicators for evaluating efficacy assessment following TACE. This review explores the roles and research progress of inflammatory factors, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), immune modulatory factors like programmed cell death receptor-1 (PD-1), angiogenic factors such as vascular endothelial growth factor (VEGF), and cell growth and differentiation factors in post-TACE efficacy assessments. Changes in these factors not only serve as early biomarkers of tumor biology and treatment response but also provide valuable prognostic information. Furthermore, a comprehensive analysis of these biomarkers provides deeper insights into the complexities and dynamic changes within the tumor microenvironment, enhancing our understanding of liver cancer treatment mechanisms. Future research should focus on the quantitative changes, interactions, and relationships of these biomarkers before and after TACE treatment. This approach aims to develop a comprehensive, multi-dimensional efficacy assessment model. This model would enable precise monitoring of treatment effectiveness, offer clinical decision-making, and facilitate personalized treatment plans to optimize outcomes, ultimately improve patient survival rates and quality of life.
- Primary liver cancer /
- Transarterial chemoembolization /
- Peripheral blood cytokines /
- Efficacy evaluation /
- Research progress

HTML全文

参考文献(40)

[1]	RUMGAY H, ARNOLD M, FERLAY J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040[J]. J Hepatol, 2022, 77(6): 1598-1606. doi: 10.1016/j.jhep.2022.08.021
[2]	BERNATZ S, ELENBERGER O, ACKERMANN J, et al. CT-radiomics and clinical risk scores for response and overall survival prognostication in TACE HCC patients[J]. Sci Rep, 2023, 13(1): 533. DOI: 10.1038/s41598-023-27714-0.
[3]	KARTIKASARI A E R, HUERTAS C S, MITCHELL A, et al. Tumor-induced inflammatory cytokines and the emerging diagnostic devices for cancer detection and prognosis[J]. Front Oncol, 2021, 11: 692142. DOI: 10.3389/fonc.2021.692142.
[4]	JUNG Y J, WOO J S, HWANG S H, et al. Effect of IL-10-producing B cells in peripheral blood and tumor tissue on gastric cancer[J]. Cell Commun Signal, 2023, 21(1): 320. DOI: 10.1186/s12964-023-01174-5.
[5]	ZHAO S M, JIANG J H, JIANG Y Y, et al. The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity[J]. Cell Death Dis, 2020, 11(1): 70. DOI: 10.1038/s41419-020-2264-z.
[6]	崔明新, 刘晓刚, 程大铭, 等. 血清微RNA-429, 肿瘤坏死因子受体相关因子6与肝癌肝动脉化疗栓塞术灵敏度相关性及槐耳颗粒干预作用研究[J]. 安徽医药, 2023, 27(6): 1144-1149. doi: 10.3969/j.issn.1009-6469.2023.06.019 CUI M X, LIU X G, CHENG D M, et al. Study on the correlation between serum miR-429, TRAF6 and TACE sensitivity of liver cancer and the intervention effect of Huaier granules[J]. Anhui Medical and Pharmaceutical Journal, 2023, 27(6): 1144-1149. doi: 10.3969/j.issn.1009-6469.2023.06.019
[7]	陈靓, 刘三海, 黄强. NFAT5在肝细胞癌中表达的临床意义及其对IL-6、TNF-α表达的调控作用[J]. 中华内分泌外科杂志, 2023, 17(6): 720-723. doi: 10.3760/cma.j.cn.115807-20220630-00174 CHEN L, LIU S H, HUANG Q. Clinical significance of NFAT5 expression in hepatocellular carcinoma and its regulatory effect on the expression of inflammatory related factors IL-6 and TNF-α[J]. Chinese Journal of Endocrine Surgery, 2023, 17(6): 720-723. doi: 10.3760/cma.j.cn.115807-20220630-00174
[8]	胡舟朝, 王和平, 严金岗, 等. 肝动脉化疗栓塞联合射频消融治疗巴塞罗那分期中晚期肝癌的预后影响因素分析[J]. 中华全科医学, 2022, 20(9): 1495-1497, 1525. doi: 10.16766/j.cnki.issn.1674-4152.002632 HU Z C, WANG H P, YAN J G, et al. Prognostic factors of transarterial chemoembolization combined with radiofrequency ablation for advanced Barcelona clinic liver cancer[J]. Chinese Journal of General Practice, 2022, 20(9): 1495-1497, 1525. doi: 10.16766/j.cnki.issn.1674-4152.002632
[9]	葛源森, 张伟, 史晓雯, 等. 自拟培元解毒通络汤治疗原发性肝癌TACE术后栓塞综合征的效果及对炎性细胞因子的影响[J]. 河北医药, 2023, 45(13): 2024-2026. doi: 10.3969/j.issn.1002-7386.2023.13.025 GE Y S, ZHANG W, SHI X W, et al. Self-made PeiyuanJieduTongluo Decoction in the treatment of primary liver cancer with embolism syndrome after transcatheter arterial chemoembolization and the regulatory effects oninflammatory cytokine levels[J]. Hebei Medical Journal, 2023, 45(13): 2024-2026. doi: 10.3969/j.issn.1002-7386.2023.13.025
[10]	龙利, 石荣书, 胡天刚, 等. TACE术联合胸腺肽α1治疗原发性肝癌并发门静脉癌栓的疗效及对免疫功能的影响[J]. 现代生物医学进展, 2021, 21(5): 923-926. LONG L, SHI R S, HU T G, et al. Effect of TACE combined with thymosinα1 on primary liver cancer complicated with portal vein tumor thrombus[J]. Progress in Modern Biomedicine, 2021, 21(5): 923-926.
[11]	王晖, 汤旻, 沈颖, 等. 中晚期原发性肝癌患者TACE术后血管内皮生长因子受体表达与疗效的关系[J]. 医学临床研究, 2021, 38(8): 1128-1131, 1135. doi: 10.3969/j.issn.1671-7171.2021.08.003 WANG H, TANG M, SHEN Y, et al. Relationship between the expression of vascular endothelial growth factor receptor and therapeutic effect in patients with advanced PHC after TACE[J]. Journal of Clinical Research, 2021, 38(8): 1128-1131, 1135. doi: 10.3969/j.issn.1671-7171.2021.08.003
[12]	ZEGEYE M M, LINDKVIST M, FǍLKER K, et al. Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells[J]. Cell Commun Signal, 2018, 16(1): 55. DOI: 10.1186/s12964-018-0268-4.
[13]	LABADIE K P, KREUSER S A, BREMPELIS K J, et al. Production of an interleukin-10 blocking antibody by genetically engineered macrophages increases cancer cell death in human gastrointestinal tumor slice cultures[J]. Cancer Gene Ther, 2023, 30(9): 1227-1233. doi: 10.1038/s41417-023-00632-z
[14]	ZHENG D H, YANG J M, WU J X, et al. Cidan capsule in combination with adjuvant transarterial chemoembolization reduces recurrence rate after curative resection of hepatocellular carcinoma: a multicenter, randomized controlled trial[J]. Chin J Integr Med, 2023, 29(1): 3-9. doi: 10.1007/s11655-022-3537-4
[15]	何亚莉, 杨志一, 强依凡, 等. 中药汤剂消癌化癖饮对原发性肝癌TACE术后患者血管生成因子及临床疗效的影响[J]. 中国医药导刊, 2022, 24(10): 998-1003. doi: 10.3969/j.issn.1009-0959.2022.10.009 HE Y L, YANG Z Y, QIANG Y F, et al. Effects of Xiaoaihuapi decoction on angiogenesis factors and clinical efficacy in patients with primary liver cancer after TACE[J]. Chinese Journal of Medicinal Guide, 2022, 24(10): 998-1003. doi: 10.3969/j.issn.1009-0959.2022.10.009
[16]	薛晨祺, 徐春阳, 姚煜, 等. 替吉奥联合阿帕替尼辅助治疗TACE术后原发性肝癌的临床观察及cfDNA与疗效的相关性[J]. 临床与病理杂志, 2022, 42(11): 2689-2698. doi: 10.3978/j.issn.2095-6959.2022.11.014 XUE C Q, XU C Y, YAO Y, et al. Clinical observation of seggio combined with apatinib in the treatment of primary liver cancer after TACE and the correlation between cfDNA and efficacy[J]. Journal of Clinical and Pathological Research, 2022, 42(11): 2689-2698. doi: 10.3978/j.issn.2095-6959.2022.11.014
[17]	WANG Y Q, DU J, GAO Z Y, et al. Evolving landscape of PD-L2: bring new light to checkpoint immunotherapy[J]. Br J Cancer, 2023, 128(7): 1196-1207. doi: 10.1038/s41416-022-02084-y
[18]	HOSSEN M M, MA Y M, YIN Z H, et al. Current understanding of CTLA-4: from mechanism to autoimmune diseases[J]. Front Immunol, 2023, 14: 1198365. DOI: 10.3389/fimmu.2023.1198365.
[19]	POKURI V K, TOMASZEWSKI G M, AIT-OUDHIA, et al. Efficacy, safety, and potential biomarkers of sunitinib and transarterial chemoembolization (TACE) combination in Advanced Hepatocellular Carcinoma (HCC): phase Ⅱ trial[J]. Am J Clin Oncol, 2018, 41(4): 332-338. doi: 10.1097/COC.0000000000000286
[20]	张英, 张雷, 丁海涛. TACE术后阿帕替尼维持治疗进展期肝细胞癌患者疗效分析[J]. 实用肝脏病杂志, 2021, 24(5): 733-736. doi: 10.3969/j.issn.1672-5069.2021.05.032 ZHANG Y, ZHANG L, DING H T. Impacting efficacy factors of apatinib maintaining treatment after transcatheter hepatic artery chemoembolization in patients with advanced hepatocellular carcinoma[J]. Journal of Practical Hepatology, 2021, 24(5): 733-736. doi: 10.3969/j.issn.1672-5069.2021.05.032
[21]	杜锋, 杨炜炜, 刘尧. 顺铂热化疗灌注联合TACE对肝癌患者疗效及肿瘤细胞因子水平的影响[J]. 贵州医药, 2021, 45(1): 27-28. DU F, YANG W W, LIU Y. Effect of cisplatin thermochemotherapy perfusion combined with TACE on curative effect and tumor cytokines levels in patients with hepatocellular carcinoma[J]. Guizhou Medical Journal, 2021, 45(1): 27-28.
[22]	JIA T, JACQUET T, DALONNEAU F, et al. FGF-2 promotes angiogenesis through a SRSF1/SRSF3/SRPK1-dependent axis that controls VEGFR1 splicing in endothelial cells[J]. BMC Biol, 2021, 19(1): 173-175. doi: 10.1186/s12915-021-01103-3
[23]	HALDER S, BASU S, LALL S P, et al. Targeting the EGFR signaling pathway in cancer therapy: what's new in 2023[J]. Expert Opin Ther Targets, 2023, 27(4): 305-324.
[24]	FU J J, SU X R, LI Z H, et al. HGF/c-MET pathway in cancer: from molecular characterization to clinical evidence[J]. Oncogene, 2021, 40(28): 4625-4651. doi: 10.1038/s41388-021-01863-w
[25]	BERA K, BRAMAN N, GUPTA A, et al. Predicting cancer outcomes with radiomics and artificial intelligence in radiology[J]. Nat Rev Clin Oncol, 2022, 19(2): 132-146. doi: 10.1038/s41571-021-00560-7
[26]	MIKSAD R A, OGASAWARA S, XIA F, et al. Liver function changes after transarterial chemoembolization in US hepatocellular carcinoma patients: the LiverT study[J]. BMC Cancer, 2019, 19(1): 795-797. doi: 10.1186/s12885-019-5989-2
[27]	范晓华, 陈存国, 管建民, 等. 原发性肝癌患者行DSA引导下肝动脉化疗栓塞后疗效评估中超声造影的价值[J]. 中华全科医学, 2022, 20(2): 294-297. doi: 10.16766/j.cnki.issn.1674-4152.002336 FAN X H, CHEN C G, GUAN J M, et al. Value of contrast-enhanced ultrasound in evaluating the efficacy of digital subtraction angiography-guided hepatic artery chemoembolisation in patients with hepatocellular carcinoma[J]. Chinese Journal of General Practice, 2022, 20(2): 294-297. doi: 10.16766/j.cnki.issn.1674-4152.002336
[28]	王昊, 单良, 吴孝雄, 等. 清肝祛癌方联合肝动脉化疗栓塞术治疗晚期热瘀型肝癌临床疗效[J]. 临床军医杂志, 2021, 49(3): 306-308. WANG H, SHAN L, WU X X, et al. Clinical efficacy of Qinggan Quai decoction combined with transcatheter arterial chemoembolization in the treatment of advanced liver cancer with heat stasis[J]. Clinical Journal of Medical Officers, 2021, 49(3): 306-308.
[29]	ROSE-JOHN S, JENKINS B J, GARBERS C, et al. Targeting IL-6 trans-signalling: past, present and future prospects[J]. Nat Rev Immunol, 2023, 23(10): 666-681. doi: 10.1038/s41577-023-00856-y
[30]	DU J, SUN J X, WEN Z P, et al. Serum IL-6 and TNF-α levels are correlated with disease severity in patients with ankylosing spondylitis[J]. Lab Med, 2022, 53(2): 149-155. doi: 10.1093/labmed/lmab029
[31]	YAMAGUCHI H, HSU J M, YANG W H, et al. Mechanisms regulating PD-L1 expression in cancers and associated opportunities for novel small-molecule therapeutics[J]. Nat Rev Clin Oncol, 2022, 19(5): 287-305. doi: 10.1038/s41571-022-00601-9
[32]	刘莹莹, 张国尊, 梁育飞, 等. 益脾养肝法联合TACE对原发性肝癌患者肝功能及巨噬细胞介导细胞因子水平的影响[J]. 湖北中医药大学学报, 2022, 24(5): 39-42. LIU Y Y, ZHANG G Z, LIANG Y F, et al. Effects of benefiting spleen and nourishing liver method combined with TACE on liver function and macrophage-mediated cytokine levels in patients with primary liver cancer[J]. Journal of Hubei University of Chinese Medicine, 2022, 24(5): 39-42.
[33]	李杰, 张玉河, 李伟, 等. 右美托咪定对原发性肝癌TACE术患者镇痛效果, 炎症因子及T淋巴细胞亚群的影响[J]. 医学临床研究, 2022, 39(11): 1615-1621. doi: 10.3969/ji.ssn.1671-7171.2022.11.005 LI J, ZHANG Y H, LI W, et al. Effects of dexmedetomidine on analgesic effect, inflammatory factors and T lymphocyte subsets in patients undergoing TACE operation for primary liver cancer[J]. Journal of Clinical Research, 2022, 39(11): 1615-1621. doi: 10.3969/ji.ssn.1671-7171.2022.11.005
[34]	HARDING J J, DO R K, YAUBIE A, et al. Phase 1b study of galunisertib and ramucirumab in patients with advanced hepatocellular carcinoma[J]. Cancer Med, 2021, 10(9): 3059-3067. doi: 10.1002/cam4.3880
[35]	LIU Z D, YU X B, XU L, et al. Current insight into the regulation of PD-L1 in cancer[J]. Exp Hematol Oncol, 2022, 11(1): 44-46. doi: 10.1186/s40164-022-00297-8
[36]	EL SHORBAGY S, ABUTALEB F, LABIB H A, et al. Prognostic significance of VEGF and HIF-1 α in hepatocellular carcinoma patients receiving sorafenib versus metformin sorafenib combination[J]. J Gastrointest Cancer, 2021, 52(1): 269-279. doi: 10.1007/s12029-020-00389-w
[37]	YI M, ZHENG X L, NIU M K, et al. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions[J]. Mol Cancer, 2022, 21(1): 28-31. doi: 10.1186/s12943-021-01489-2
[38]	ZHU H D, LI H L, HUANG M S, et al. Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001)[J]. Signal Transduct Target Ther, 2023, 8(1): 58-60. doi: 10.1038/s41392-022-01235-0
[39]	RAOUL J L, FORNER A, BOLONDI L, et al. Updated use of TACE for hepatocellular carcinoma treatment: how and when to use it based on clinical evidence[J]. Cancer Treat Rev, 2019, 72(1): 28-36.
[40]	王满周, 段旭华, 韩新巍, 等. TACE术中应用CalliSpheres载药栓塞微球治疗不可切除肝癌出现"血管湖"的意义及应对措施[J]. 临床放射学杂志, 2022, 41(6): 1132-1138. WANG M Z, DUAN X H, HAN X W, et al. The significance and countermeasures of vascular lake during callispheres drug-eluting bead transcatheter arterial chemoembolization treating unresectable hepatocellular carcinoma[J]. Journal of Clinical Radiology, 2022, 41(6): 1132-1138.