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早期上皮性卵巢癌的预后分层增强:中性粒细胞与淋巴细胞比值的多组织学分析,特别关注透明细胞组织学

Enhanced prognostic stratification in early-stage epithelial ovarian cancer: multi-histological analysis of neutrophil-to-lymphocyte ratio with particular emphasis on clear cell histology.

作者信息

Sung En-Ling, Lin Hao, Ou Yu-Che, Fu Hung-Chun, Lin Mei-Yi, Kao Chien-Hsiang, Wu Chen-Hsuan, Changchien Chan-Chao

机构信息

Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 833, Taiwan.

Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University Taoyuan 33302, Taiwan.

出版信息

Am J Cancer Res. 2025 Aug 25;15(8):3632-3644. doi: 10.62347/BETA4769. eCollection 2025.

Abstract

In Asian populations, early-stage ovarian cancers account for approximately half of cases, substantially exceeding proportions observed in Western cohorts, with clear cell carcinoma (CCC) and endometrioid carcinoma (EMC) demonstrating markedly higher prevalence in Asian women. The tumor immune microenvironment critically influences oncological progression, and systemic inflammatory biomarkers can serve as surrogates of host immunological responses. This study evaluated the prognostic value of the neutrophil-to-lymphocyte ratio (NLR), an established index of systemic inflammation and immune dysregulation, across histologic subtypes in early-stage epithelial ovarian cancer. We retrospectively analyzed patients with FIGO stage I-II epithelial ovarian cancer diagnosed between 2011 and 2018. Pretreatment NLR was calculated to reflect the balance between neutrophil-driven inflammation and lymphocyte-mediated immunity. Among 217 enrolled patients, CCC (28.1%) and EMC (34.6%) constituted the predominant histotypes, consistent with Asian demographic patterns. In univariable analyses, elevated NLR and advanced stage significantly correlated with diminished progression-free survival (HR 5.04, P<0.001; HR 3.81, P<0.001) and overall survival (HR 4.54, P=0.013; HR 3.91, P=0.003). In multivariable models, NLR remained an independent prognostic factor for both endpoints (PFS: HR 5.38, P=0.001; OS: HR 4.27, P=0.048). Histology-stratified analyses revealed distinctive immunological signatures, with elevated NLR in CCC patients exhibiting exceptionally strong prognostic value (univariable PFS: HR 8.14, P=0.001; OS: HR 22.42, P=0.005; multivariable PFS: HR 8.00, P=0.007; OS: HR 32.43, P=0.025), providing information beyond FIGO stage. Conversely, NLR demonstrated no prognostic relevance in EMC patients, indicating heterogeneous immune microenvironments across histological variants. Elevated pre-treatment NLR independently predicts adverse outcomes in early-stage epithelial ovarian cancer, with particularly pronounced prognostic utility in CCC. These findings may be especially relevant in Asian populations, in which CCC is more common, and could inform personalized risk stratification.

摘要

在亚洲人群中,早期卵巢癌约占病例总数的一半,大大超过了西方队列中的比例,其中透明细胞癌(CCC)和子宫内膜样癌(EMC)在亚洲女性中的患病率明显更高。肿瘤免疫微环境对肿瘤进展具有关键影响,全身炎症生物标志物可作为宿主免疫反应的替代指标。本研究评估了中性粒细胞与淋巴细胞比值(NLR)作为一种已确立的全身炎症和免疫失调指标,在早期上皮性卵巢癌不同组织学亚型中的预后价值。我们回顾性分析了2011年至2018年间诊断为FIGO I-II期上皮性卵巢癌的患者。计算治疗前的NLR以反映中性粒细胞驱动的炎症和淋巴细胞介导的免疫之间的平衡。在217名入组患者中,CCC(28.1%)和EMC(34.6%)构成主要组织学类型,与亚洲人口模式一致。在单变量分析中,NLR升高和晚期与无进展生存期缩短(HR 5.04,P<0.001;HR 3.81,P<0.001)和总生存期缩短(HR 4.54,P=0.013;HR 3.91,P=0.003)显著相关。在多变量模型中,NLR仍然是两个终点的独立预后因素(PFS:HR 5.38,P=0.001;OS:HR 4.27,P=0.048)。组织学分层分析揭示了独特的免疫特征,CCC患者中NLR升高具有特别强的预后价值(单变量PFS:HR 8.14,P=0.001;OS:HR 22.42,P=0.005;多变量PFS:HR 8.00,P=0.007;OS:HR 32.43,P=0.025),提供了超出FIGO分期的信息。相反,NLR在EMC患者中无预后相关性,表明不同组织学变体的免疫微环境存在异质性。治疗前NLR升高独立预测早期上皮性卵巢癌的不良结局,在CCC中预后效用尤为显著。这些发现可能在CCC更为常见的亚洲人群中尤为相关,并可为个性化风险分层提供依据。

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