Predictive Value of Pyroptosis Markers (NLRP3, HMGB1, and Caspase-1) in the Prognosis of Patients With Metastatic Breast Cancer: A Prospective Observational Study

IF 2.4 4区医学 Q3 OBSTETRICS & GYNECOLOGY Breast Journal Pub Date : 2025-12-30 DOI:10.1155/tbj/8821116

Yi Zhang, Ying He, Qiang Liu, Hongwu Deng

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Abstract

Objective

The predictive value of serum pyroptosis markers, including NOD-like receptor family pyrin domain containing 3 (NLRP3), high mobility group box 1 (HMGB1), and caspase-1, in metastatic breast cancer (MBC) patients was investigated.

Methods

A prospective observational study was conducted, enrolling MBC patients who had not undergone prior radiotherapy or chemotherapy. Serum levels of pyroptosis markers (NLRP3, HMGB1, and caspase-1) and conventional tumor markers, including carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and cancer antigen 15-3 (CA15-3), were measured using enzyme-linked immunosorbent assay (ELISA) kits. Demographic and clinical data were collected, including age, tumor size, hormone receptor status, and metastatic sites. Patients were followed up for 24 months, and overall survival (OS) was recorded.

Results

The study included 122 MBC patients, categorized into the favorable and poor prognosis groups based on 24-month survival. Elevated levels of NLRP3 and HMGB1 were significantly associated with poor prognosis, whereas lower levels of caspase-1 were observed in patients with unfavorable outcomes. Receiver operating characteristic (ROC) curve analysis demonstrated that pyroptosis markers, particularly caspase-1, had significant predictive value for MBC prognosis. Kaplan–Meier curves showed that patients with high HMGB1 levels had a shorter 24-month OS, whereas those with low caspase-1 levels also exhibited a shorter 24-month OS. Multivariate logistic regression analysis identified tumor diameter, Ki67, molecular subtype, number of metastatic sites per patient, and HMGB1 were independent risk factors for poor prognosis in MBC patients, whereas caspase-1 was an independent protective factor against poor prognosis.

Conclusion

Serum pyroptosis markers (HMGB1 and caspase-1) were valuable prognostic indicators in MBC patients. Elevated HMGB1 levels, along with reduced caspase-1 levels, were associated with poorer outcomes.

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NLRP3、HMGB1和Caspase-1在转移性乳腺癌患者预后中的预测价值：一项前瞻性观察研究

目的：探讨nod样受体家族pyrin结构域3 （NLRP3）、高迁移率组盒1 （HMGB1）、caspase-1在转移性乳腺癌（MBC）患者血清焦亡标志物的预测价值。方法：进行前瞻性观察研究，纳入未接受过放疗或化疗的MBC患者。采用酶联免疫吸附试验（ELISA）试剂盒检测血清焦亡标志物（NLRP3、HMGB1和caspase-1）和常规肿瘤标志物（癌胚抗原（CEA）、癌抗原125 （CA125）和癌抗原15-3 (CA15-3)）水平。收集了人口统计学和临床数据，包括年龄、肿瘤大小、激素受体状态和转移部位。随访24个月，记录总生存期（OS）。结果：本研究纳入122例MBC患者，根据24个月生存率分为预后良好组和预后不良组。NLRP3和HMGB1水平升高与预后不良显著相关，而caspase-1水平较低的患者预后不良。受试者工作特征（ROC）曲线分析表明，焦亡标志物，特别是caspase-1，对MBC预后有显著的预测价值。Kaplan-Meier曲线显示，高HMGB1水平的患者24个月的生存期较短，而低caspase-1水平的患者24个月的生存期也较短。多因素logistic回归分析发现肿瘤直径、Ki67、分子亚型、患者转移位点数、HMGB1是MBC患者预后不良的独立危险因素，而caspase-1是预后不良的独立保护因素。结论：血清焦亡标志物HMGB1和caspase-1是判断MBC患者预后的重要指标。HMGB1水平升高以及caspase-1水平降低与预后较差相关。

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来源期刊

Breast Journal 医学-妇产科学

CiteScore

4.00

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： The Breast Journal is the first comprehensive, multidisciplinary source devoted exclusively to all facets of research, diagnosis, and treatment of breast disease. The Breast Journal encompasses the latest news and technologies from the many medical specialties concerned with breast disease care in order to address the disease within the context of an integrated breast health care. This editorial philosophy recognizes the special social, sexual, and psychological considerations that distinguish cancer, and breast cancer in particular, from other serious diseases. Topics specifically within the scope of The Breast Journal include: Risk Factors Prevention Early Detection Diagnosis and Therapy Psychological Issues Quality of Life Biology of Breast Cancer.