D-二聚体与接受PD-1/PD-L1抑制剂治疗的晚期肿瘤患者长期预后的关系:一项Meta分析

doi:10.3969/j.issn.1004-583X.2025.02.001

摘要/Abstract

摘要：

目的本研究旨在分析治疗前D-二聚体水平和接受PD-1/PD-L1抑制剂治疗的晚期肿瘤患者长期预后的关系。方法在中国知网、万方、维普、Pubmed、Web of Science、Cochrane Library等数据库检索截止至2024年10月20日发表的相关文献,最终纳入6篇文献进行分析。结果在接受PD-1/PD-L1抑制剂治疗的晚期肿瘤患者中,与正常D-二聚体水平的患者相比,高D-二聚体水平患者的无进展生存期(progression free survival,PFS)(单因素分析:HR=1.89,95%CI:1.33~2.67,P=0.0004;多因素分析:HR=1.79, 95%CI:1.18~2.72,P=0.006)和总生存期(overall survival,OS)显著缩短(单因素分析:HR=2.02,95%CI:1.60~2.56,P<0.00001;多因素分析:HR=2.08,95%CI:1.63~2.65,P<0.00001)。结论 D-二聚体可作为预测接受PD-1/PD-L1抑制剂治疗肿瘤患者预后的潜在生物标志物。

关键词: D-二聚体, 免疫治疗, 预后, 生物标志物

Abstract:

Objective The study aims to analyze the associations between pretreatment D-dimer (D-D) levels and the long-term prognosis of advanced cancer patients receiving programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. Methods Relevant literatures published up to October 20, 2024, were retrieved from databases including China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Pubmed, Web of Science, and Cochrane Library. Six literatures were ultimately included in the analysis. Results The advanced cancer patients receiving PD-1/PD-L1 inhibitors with high D-D levels had significantly shorter progression free survival (PFS) (univariate analysis: HR=1.89, 95%CI: 1.33-2.67, P=0.0004; multivariate analysis: HR=1.79, 95%CI: 1.18-2.72, P=0.006) and overall survival (OS) (univariate analysis: HR=2.02, 95%CI: 1.60-2.56, P<0.00001; multivariate analysis: HR=2.08, 95%CI: 1.63-2.65, P<0.00001) than those with normal D-D levels. Conclusion D-D may serve as a potential biomarker for predicting the prognosis of advanced cancer patients receiving PD-1/PD-L1 inhibitors.

Key words: D-dimer, immunotherapy, prognosis, biomarker

中图分类号:

R730.51

叶倩, 刘申香. D-二聚体与接受PD-1/PD-L1抑制剂治疗的晚期肿瘤患者长期预后的关系:一项Meta分析[J]. 临床荟萃, 2025, 40(2): 101-106.

Ye Qian, Liu Shenxiang. Association between D-dimer and the long-term prognosis of advanced cancer patients receiving PD-1/PD-L1 inhibitors: A meta-analysis[J]. Clinical Focus, 2025, 40(2): 101-106.

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链接本文: https://lchc.magtechjournal.com/CN/10.3969/j.issn.1004-583X.2025.02.001

https://lchc.magtechjournal.com/CN/Y2025/V40/I2/101

图/表 6

参考文献 22

[1]	Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022[J]. CA Cancer J Clin, 2022, 72(1):7-33.
[2]	Jiang Y, Zhao X, Fu J, et al. Progress and challenges in precise treatment of tumors with PD-1/PD-L1 blockade[J]. Front Immunol, 2020, 11:339. doi: 10.3389/fimmu.2020.00339 pmid: 32226426
[3]	Pang K, Shi ZD, Wei LY, et al. Research progress of therapeutic effects and drug resistance of immunotherapy based on PD-1/PD-L1 blockade[J]. Drug Resist Updat, 2023, 66:100907.
[4]	Ma M, Cao R, Wang W, et al. The D-dimer level predicts the prognosis in patients with lung cancer: A systematic review and meta-analysis[J]. J Cardiothorac Surg, 2021, 16(1):243. doi: 10.1186/s13019-021-01618-4 pmid: 34454552
[5]	Shang X, Li X. D-dimer and the short-term prognosis of patients with subarachnoid hemorrhage: A meta-analysis[J]. Eur Neurol, 2024, 87(4):188-202.
[6]	Li W, Tang Y, Song Y, et al. Prognostic role of pretreatment plasma d-dimer in patients with solid tumors: A systematic review and meta-analysis[J]. Cell Physiol Biochem, 2018, 45(4):1663-1676. doi: 10.1159/000487734 pmid: 29490291
[7]	Liu T, Tang LV. Incidence and risk factors of venous and arterial thromboembolism in immune checkpoint inhibitor therapy[J]. Curr Pharm Des, 2022, 28(36):2950-2952.
[8]	Moik F, Chan WE, Wiedemann S, et al. Incidence, risk factors, and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy[J]. Blood, 2021, 137(12):1669-1678. doi: 10.1182/blood.2020007878 pmid: 33067632
[9]	Wei XY, Zhang CC, Zang FL, et al. Preliminary study on inflammatory markers for predicting the efficacy and prognosis of anti-PD-1 antibody treatment in patients with non-small cell lung cancer[J]. Chin J Clin Oncol, 2021, 48(11):547-551.
[10]	Zhang W, Zhang Z, Lou S, et al. Efficacy, safety and predictors of combined fruquintinib with programmed death-1 inhibitors for advanced microsatellite-stable colorectal cancer: A retrospective study[J]. Frontiers in oncology, 2022, 12:929342.
[11]	Li X, Lu D, Zhang Z, et al. Prognostic value of plasma D-dimer levels in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: A retrospective study[J]. J Thorac Dis, 2022, 14(10):4125-4135. doi: 10.21037/jtd-22-1363 pmid: 36389301
[12]	Chen C, Yin H, Zhang Y, et al. Plasma D-dimer and interleukin-6 are associated with treatment response and progression-free survival in advanced NSCLC patients on anti-PD-1 therapy[J]. Cancer Med, 2023, 12(15):15831-15840.
[13]	Sun W, Yao XM, Wang PJ, et al. Exploration of prognostic factors and nomogram construction for advanced non-small cell lung cancer treated with immunotherapy based on hematologic indexes[J]. J Int Oncol, 2024, 51(3):143-150.
[14]	Wu Y, Liu X, Li H, et al. D-dimer levels predict the treatment efficacy and prognosis of esophageal squamous cell carcinoma treated with PD-1/PD-L1 inhibitors[J]. Int J Biol Markers, 2024, 39(3):209-216.
[15]	Wu B, Zhang G, Zhao X, et al. Association between D-dimer levels and clinicopathological characteristics of pancreatic cancer and its role in prognosis: A systematic review and meta-analysis[J]. Asian J Surg, 2024, 47(8):3417-3424.
[16]	Zhou YX, Yang ZM, Feng J, et al. High plasma D-dimer level is associated with decreased survival in patients with lung cancer: A meta-analysis[J]. Tumour Biol, 2013, 34(6):3701-3704.
[17]	Alkhoder L, Salamoon M, Saifo M, et al. D-dimer as a predictive biomarker of response to chemotherapy in patients with metastatic breast cancer[J]. Biomark Insights, 2024, 19:11772719241290704.
[18]	Singh AK, Malviya R. Coagulation and inflammation in cancer: Limitations and prospects for treatment[J]. Biochim Biophys Acta Rev Cancer, 2022, 1877(3):188727.
[19]	Kawashima S, Togashi Y. Resistance to immune checkpoint inhibitors and the tumor microenvironment[J]. Exp Dermatol, 2023, 32(3):240-249.
[20]	Kleinegris MC, ten Cate H, ten Cate-Hoek AJ. D-dimer as a marker for cardiovascular and arterial thrombotic events in patients with peripheral arterial disease. A systematic review[J]. Thromb Haemost, 2013, 110(2):233-243.
[21]	Zhang W, Zhang Z, Lou S, et al. Efficacy, safety and predictors of combined fruquintinib with programmed death-1 inhibitors for advanced microsatellite-stable colorectal cancer: A retrospective study[J]. Front Oncol, 2022, 12:929342.
[22]	Chen C, Li J, Li J, et al. Application of an elevated plasma D-dimer cut-off value improves prognosis prediction of advanced non-small cell lung cancer[J]. Ann Transl Med, 2020, 8(18):1153. doi: 10.21037/atm-20-5947 pmid: 33241002

第一作者	发表年份	研究类型	肿瘤类型			患者数量	年龄(岁, 中位数,范围)		PD-1/PD-L1 抑制剂类型		D-二聚体检测时间
Wei等^[9]	2021	回顾性	晚期NSCLC			64	-		帕博利珠单抗		治疗前、最佳缓解期、疾病进展期
Zhang等^[10]	2022	回顾性	晚期MSS/pM MR CRC			110	53(22-81)		信迪利单抗、卡瑞利珠单抗、特瑞普利单抗、替雷利珠单抗、帕博利珠单抗		治疗前
Li等^[11]	2022	回顾性	晚期NSCLC			277	61(33-91)		-		治疗前
Chen等^[12]	2023	回顾性	晚期或复发 NSCLC			100	D-二聚体<0.98 mg/L:63(57-68);E-D-二聚体≥0.98 mg/L:64(54.5-68)		纳武利尤单抗、信迪利单抗、卡瑞利珠单抗、帕博利珠单抗		治疗前
Sun等^[13]	2024	回顾性	晚期NSCLC			80	63(34-73)		信迪利单抗、卡瑞利珠单抗、特瑞普利单抗		治疗前、最佳缓解期、疾病进展期
Wu等^[14]	2024	回顾性	晚期或转移性ESCC			233	-		-		治疗前
第一作者	D-二聚体截断值(mg/L)			生存结局	单因素分析(HR,95%CI)					多因素分析(HR,95%CI)
第一作者	D-二聚体截断值(mg/L)			生存结局	OS			PFS		OS		PFS
Wei等^[9]	1.51			PFS	-			-		-		1.72(0.59~5.00)
Zhang等^[10]	0.30			PFS	-			1.71(1.09~2.70)		-		1.28(0.80~2.04)
Li等^[11]	0.50			OS、PFS	2.29(1.52~3.46)			1.80(1.30~2.49)		2.13(1.40~3.25)		1.84(1.32~2.56)
Chen等^[12]	0.98			PFS	-			7.37(2.53~21.51)		-		14.09(3.26~60.84)
Sun等^[13]	-			OS	1.00(1.00~1.00)			-		-		-
Wu等^[14]	0.24			OS、PFS	1.90(1.42~2.53)			1.51(1.15~1.98)		2.05(1.52~2.76)		1.52(1.15~2.03)

第一作者	发表年份	研究类型	肿瘤类型			患者数量	年龄(岁, 中位数,范围)		PD-1/PD-L1 抑制剂类型		D-二聚体检测时间
Wei等^[9]	2021	回顾性	晚期NSCLC			64	-		帕博利珠单抗		治疗前、最佳缓解期、疾病进展期
Zhang等^[10]	2022	回顾性	晚期MSS/pM MR CRC			110	53(22-81)		信迪利单抗、卡瑞利珠单抗、特瑞普利单抗、替雷利珠单抗、帕博利珠单抗		治疗前
Li等^[11]	2022	回顾性	晚期NSCLC			277	61(33-91)		-		治疗前
Chen等^[12]	2023	回顾性	晚期或复发 NSCLC			100	D-二聚体<0.98 mg/L:63(57-68);E-D-二聚体≥0.98 mg/L:64(54.5-68)		纳武利尤单抗、信迪利单抗、卡瑞利珠单抗、帕博利珠单抗		治疗前
Sun等^[13]	2024	回顾性	晚期NSCLC			80	63(34-73)		信迪利单抗、卡瑞利珠单抗、特瑞普利单抗		治疗前、最佳缓解期、疾病进展期
Wu等^[14]	2024	回顾性	晚期或转移性ESCC			233	-		-		治疗前
第一作者	D-二聚体截断值(mg/L)			生存结局	单因素分析(HR,95%CI)					多因素分析(HR,95%CI)
第一作者	D-二聚体截断值(mg/L)			生存结局	OS			PFS		OS		PFS
Wei等^[9]	1.51			PFS	-			-		-		1.72(0.59~5.00)
Zhang等^[10]	0.30			PFS	-			1.71(1.09~2.70)		-		1.28(0.80~2.04)
Li等^[11]	0.50			OS、PFS	2.29(1.52~3.46)			1.80(1.30~2.49)		2.13(1.40~3.25)		1.84(1.32~2.56)
Chen等^[12]	0.98			PFS	-			7.37(2.53~21.51)		-		14.09(3.26~60.84)
Sun等^[13]	-			OS	1.00(1.00~1.00)			-		-		-
Wu等^[14]	0.24			OS、PFS	1.90(1.42~2.53)			1.51(1.15~1.98)		2.05(1.52~2.76)		1.52(1.15~2.03)

亚组	单因素分析			亚组	多因素分析
亚组	文献数量	HR(95%CI)	P	亚组	文献数量	HR(95%CI)	P
肿瘤类型				肿瘤类型
NSCLC	2	3.31(0.84~13.00)	0.09	NSCLC	2	4.47(0.62~32.34)	0.14
CRC	1	1.71(1.08~2.70)	0.02	CRC	1	1.28(0.80~2.03)	0.30
ESCC	1	1.51(1.15~1.98)	0.003	ESCC	1	1.52(1.14~2.03)	0.004
D-二聚体截断值(mg/L)				D-二聚体截断值(mg/L)
<0.5	2	1.56(1.23~1.97)	0.0002	<0.5	2	1.45(1.14~1.85)	0.003
≥0.5	2	3.31(0.84~13.00)	0.09	≥0.5	2	4.47(0.62~32.34)	0.14

亚组	单因素分析			亚组	多因素分析
亚组	文献数量	HR(95%CI)	P	亚组	文献数量	HR(95%CI)	P
肿瘤类型				肿瘤类型
NSCLC	2	3.31(0.84~13.00)	0.09	NSCLC	2	4.47(0.62~32.34)	0.14
CRC	1	1.71(1.08~2.70)	0.02	CRC	1	1.28(0.80~2.03)	0.30
ESCC	1	1.51(1.15~1.98)	0.003	ESCC	1	1.52(1.14~2.03)	0.004
D-二聚体截断值(mg/L)				D-二聚体截断值(mg/L)
<0.5	2	1.56(1.23~1.97)	0.0002	<0.5	2	1.45(1.14~1.85)	0.003
≥0.5	2	3.31(0.84~13.00)	0.09	≥0.5	2	4.47(0.62~32.34)	0.14