Prognostic significance of serum complement activation, neutrophil extracellular traps and extracellular DNA in newly diagnosed epithelial ovarian cancer

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology Pub Date : 2025-02-01 DOI:10.1016/j.ygyno.2024.12.006

Jason Ricciuti , Qian Liu , A.N.M. Nazmul H. Khan , Janine M. Joseph , Bert Veuskens , Thejaswini Giridharan , Sora Suzuki , Tiffany Emmons , Michael Yaffe , Taco W. Kuijpers , Ilse Jongerius , Mieke Brouwer , Richard B. Pouw , Kunle Odunsi , Peter Frederick , Katherine LaVigne Mager , Shashikant Lele , Nicole Gaulin , Christiane Hakim , Robert P. Edwards , Brahm Segal

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引用次数: 0

Abstract

Purpose

We observed that the tumor microenvironment (TME) in metastatic epithelial ovarian cancer (EOC) and in other solid tumors can reprogram normal neutrophils to acquire a complement-dependent suppressor phenotype characterized by inhibition of stimulated T cell activation. This study aims to evaluate whether serum markers of neutrophil activation and complement at diagnosis of EOC would be associated with clinical outcomes.

Experimental design

We conducted a two-center prospective study of patients with newly diagnosed EOC (N = 188). Blood and ascites fluid were collected at diagnosis for biomarker analysis. Patients were evaluated for progression-free survival (PFS) and overall survival (OS).

Results

The median OS was 47 months (95 % CI: 34–58) and the median PFS was 12 months (95 % CI: 11–15). Pre-treatment serum levels of genomic DNA (gDNA), markers of neutrophil degranulation (myeloperoxidase [MPO]) and neutrophil extracellular traps (NETs) (citrullinated histone H3 [CitH3]), and complement activation (C3b/c) were each associated with worse OS in univariate analysis. In multivariate analyses controlling for age, stage, and optimal debulking, serum gDNA, MPO, and CitH3 remained associated with worse OS, while C3b/c levels were not. In an exploratory analysis, the largest magnitude of difference in 2-year OS occurred in patients with low C3b/c and low CitH3 compared to all other patients (87 % vs 46 % survival, respectively). In ascites fluid, increased factor H, a negative regulator of complement activation, was associated with improved OS in univariate analysis.

Conclusions

These results point to serum gDNA, NETs, and complement activation as potential prognostic biomarkers in patients with newly diagnosed EOC.

查看原文本刊更多论文

血清补体激活、中性粒细胞胞外陷阱和细胞外DNA在新诊断的上皮性卵巢癌中的预后意义。

目的：我们观察到转移性上皮性卵巢癌（EOC）和其他实体肿瘤中的肿瘤微环境（TME）可以重编程正常中性粒细胞，以获得补体依赖性抑制表型，其特征是抑制受刺激的T细胞活化。本研究旨在评估诊断EOC时中性粒细胞活化和补体的血清标志物是否与临床结果相关。实验设计：我们对新诊断的EOC患者（N = 188）进行了一项双中心前瞻性研究。诊断时采集血液和腹水进行生物标志物分析。评估患者的无进展生存期（PFS）和总生存期（OS）。结果：中位OS为47个月（95% CI: 34-58），中位PFS为12个月（95% CI: 11-15）。在单变量分析中，治疗前血清基因组DNA （gDNA）水平、中性粒细胞脱粒（髓过氧化物酶[MPO]）和中性粒细胞胞外陷阱（NETs）（瓜氨酸组蛋白H3 [CitH3]）和补体激活（C3b/c）均与较差的OS相关。在控制年龄、分期和最佳减容的多变量分析中，血清gDNA、MPO和CitH3仍然与较差的OS相关，而C3b/c水平则无关。在一项探索性分析中，与所有其他患者相比，低C3b/c和低CitH3患者的2年OS差异最大（分别为87%和46%）。在腹水中，在单变量分析中，补体激活的负调节因子H的增加与OS的改善有关。结论：这些结果表明血清gDNA、NETs和补体激活是新诊断的EOC患者潜在的预后生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gynecologic oncology 医学-妇产科学

CiteScore

8.60

自引率

6.40%

发文量

1062

审稿时长

37 days

期刊介绍： Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published. Research Areas Include: • Cell and molecular biology • Chemotherapy • Cytology • Endocrinology • Epidemiology • Genetics • Gynecologic surgery • Immunology • Pathology • Radiotherapy