术前NLR和PLR在HER2低表达乳腺癌患者中的预后意义

Prognostic significance of preoperative neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in HER2-low breast cancer

摘要

目的：旨在评估术前外周血中性粒细胞/淋巴细胞比值（NLR）与血小板/淋巴细胞比值（PLR）对人表皮生长因子受体2（HER2）低表达乳腺癌患者预后的预测意义。方法：共纳入438例患者，通过受试者工作特征（ROC）曲线确定NLR与PLR的最佳截断值分别为2.82和140.37。据此将患者划分为低NLR组（NLR<2.82）与高NLR组（NLR≥2.82），以及低PLR组（PLR<140.37）与高PLR组（PLR≥140.37）。进一步分析NLR和PLR与患者临床病理特征及生存结局的相关性，采用χ ²检验进行单因素分析，运用Kaplan-Meier法进行生存分析，并通过Cox比例风险回归模型筛选影响预后的独立因素。结果：ROC曲线分析显示，NLR对HER2低表达乳腺癌复发具有较好的预测价值（AUC=0.792），最佳临界值为2.82；PLR的AUC为0.629，临界值为140.37。复发组NLR、PLR及中性粒细胞水平显著高于未复发组（P<0.001），淋巴细胞水平显著低于未复发组（P<0.001）。不同分子亚型（Luminal A、Luminal B、三阴性）间的NLR与PLR差异无统计学意义（P>0.05），且高、低NLR/PLR组分子亚型的分布差异也无统计学意义（P>0.05）。多因素Cox回归分析显示，NLR是影响HER2低表达乳腺癌患者无病生存期的独立危险因素（P<0.001），而PLR未显示独立预测价值（P=0.262）。高NLR组5年生存率显著低于低NLR组（49.5%比89.7%，P<0.001）。结论：术前NLR是HER2低表达乳腺癌患者预后的独立预测因子，高NLR与不良预后显著相关。PLR在多因素分析中未显示独立预测价值。NLR及PLR在不同分子亚型中的分布无显著差异，提示其预后价值可能独立于分子分型。NLR作为一种简便、经济的炎症标志物，在HER2低表达乳腺癌的预后评估中具有潜在的临床应用价值。

Abstract

Objective: To evaluate the prognostic significance of preoperative peripheral blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer. Methods: A total of 438 patients were enrolled. The optimal cut-off values of NLR and PLR, determined by receiver operating characteristic (ROC) curve analysis, were 2.82 and 140.37, respectively. Accordingly, patients were divided into a low NLR group (NLR<2.82) and a high NLR group (NLR≥2.82), as well as a low PLR group (PLR<140.37) and a high PLR group (PLR≥140.37). The correlations of NLR and PLR with clinicopathological characteristics and survival outcomes were further analyzed. Univariate analysis was performed using the χ² test, survival analysis was conducted with the Kaplan-Meier method, and independent prognostic factors were identified by the Cox proportional hazards regression model. Results: ROC curve analysis showed that NLR had good predictive value for recurrence of HER2-low breast cancer (AUC=0.792), with an optimal cut-off of 2.82; the AUC of PLR was 0.629, with a cut-off of 140.37. The NLR, PLR, and neutrophil levels in the recurrence group were significantly higher than those in the non-recurrence group (P<0.001), while the lymphocyte level was significantly lower (P<0.001). There were no statistically significant differences in NLR and PLR among different molecular subtypes (Luminal A, Luminal B, triple-negative) (P>0.05), and the distribution of the high/low NLR and PLR groups among molecular subtypes was also not statistically significant (P>0.05). Multivariate Cox regression analysis further confirmed that NLR was an independent risk factor for disease-free survival in HER2-low breast cancer patients (P<0.001), whereas PLR showed no independent predictive value (P=0.262). The 5-year survival rate of the high NLR group (≥ 2.82) was significantly lower than that of the low NLR group (49.5% vs. 89.7%, P<0.001). Conclusion: Preoperative NLR is an independent predictor of prognosis in patients with HER2-low breast cancer, and a high NLR is significantly associated with poor prognosis. PLR did not prove to be an independent factor in multivariate analysis. The distribution of NLR and PLR across different molecular subtypes did not differ significantly, suggesting that their prognostic value may be independent of molecular classification. NLR, as a simple and economical inflammatory marker, has potential clinical application in the prognostic assessment of HER2-low breast cancer.

关键词

HER2低表达乳腺癌 / 中性粒细胞/淋巴细胞比值 / 血小板/淋巴细胞比值 / 临床病理特征 / 预后

Key words

HER2-low breast cancer / Neutrophil-to-lymphocyte ratio / Platelet-to-lymphocyte ratio / Clinicopathological characteristics / Prognosis

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基金资助

国家自然科学基金(82072909)

2019年度江苏省第五期“333工程”科研项目资助计划(BRA2019182)

江苏省第十六批“六大人才高峰”高层次人才选拔培养资助计划(YY-217)