血清分泌型丛生蛋白、可溶性神经纤毛蛋白1与乳腺癌改良根治术后局部复发以及预后的关系分析

Analysis of the relationship between serum secretory clusterin,soluble neuropilin-1,and local recurrence as well as prognosis after modified radical mastectomy for breast cancer

摘要

目的 探讨血清分泌型丛生蛋白(sCLU)、可溶性神经纤毛蛋白1(sNRP-1)与乳腺癌改良根治术后局部复发以及预后的关系。方法 选取2019年5月至2022年5月我院收治的235例接受改良根治手术的乳腺癌患者,术前检测血清sCLU、sNRP-1水平,术后定期随访,记录局部复发及总生存(OS)。Pearson相关分析两指标关联性,Cox回归筛选复发及OS的独立影响因素,Kaplan-Meier法绘制生存曲线。结果 肿瘤最大径≥2.5 cm、WHO组织学分级Ⅲ级、TNM分期Ⅲ期、淋巴结转移患者的血清sCLU、sNRP-1水平高于肿瘤最大径<2.5 cm、WHO组织学分级Ⅰ~Ⅱ级、TNM分期Ⅰ~Ⅱ期、无淋巴结转移患者(t/F=10.709、21.231、115.782、150.973、55.448、277.099、12.935、23.726,P<0.05)。复发组血清sCLU、sNRP-1水平高于未复发组(t=22.937、17.460,P<0.05)。乳腺癌患者血清sCLU与sNRP-1之间呈正相关(r=0.567,P<0.05)。多因素Cox回归显示高水平sCLU(HR=1.324,95%CI:1.032~2.735)、高水平sNRP-1(HR=1.506,95%CI:1.354~4.043)、淋巴结转移(HR=1.902,95%CI:1.432~4.963)、TNM分期Ⅲ期(HR=1.603,95%CI:1.241~4.035)是乳腺癌患者术后复发的危险因素(P<0.05)。高水平sCLU组3年OS率低于低水平sCLU组(62.39% vs. 87.07%,Log-ranχ²=19.330,P<0.05),高水平sNRP-1组3年OS率低于低水平sNRP-1组(60.87% vs.88.14%,Log-rankχ²=23.331,P<0.05)。多因素Cox回归显示高水平sCLU(HR=1.805,95%CI:1.532~4.841)、高水平sNRP-1(HR=1.653,95%CI:1.214~4.217)、淋巴结转移(HR=1.824,95%CI:1.702~5.362)、术后复发(HR=2.241,95%CI:1.893~6.382)是影响患者预后的危险因素(P<0.05)。结论 乳腺癌患者血清sCLU与sNRP-1水平增高与改良根治术后复发以及预后不良有关,有可能作为评估术后复发及生存预后的潜在生物标志物。

Abstract

Objective To investigate the relationship between serum secretory clusterin (sCLU),soluble neuropilin-1 (sNRP-1),and local recurrence as well as prognosis after modified radical mastectomy for breast cancer. Methods A total of 235 breast cancer patients who underwent modified radical mastectomy at our hospital from May 2019 to May 2022 were enrolled.Preoperative serum levels of sCLU and sNRP-1 were measured,and all patients were regularly followed up postoperatively,with local recurrence and overall survival (OS) recorded.Pearson correlation analysis was used to assess the correlation between the two biomarkers.Cox regression analysis was performed to identify independent risk factors for local recurrence and OS,and Kaplan-Meier method was used to plot survival curves. Results Patients with a maximum tumor diameter ≥2.5 cm,WHO histological grade Ⅲ,TNM stage Ⅲ,and lymph node metastasis had higher serum sCLU and sNRP-1 levels than those with a maximum tumor diameter <2.5 cm,WHO histological grade Ⅰ-Ⅱ,TNM stage Ⅰ-Ⅱ,and no lymph node metastasis (t/F=10.709,21.231,115.782,150.973,55.448,277.099,12.935 and 23.726,respectively,P<0.05).Serum sCLU and sNRP-1 levels in the recurrence group were higher than those in the non-recurrence group (t=22.937 and 17.460,respectively,P<0.05).A positive correlation was observed between serum sCLU and sNRP-1 levels in breast cancer patients (r=0.567,P<0.05).Multivariate Cox regression analysis revealed that high sCLU levels (HR=1.324,95%CI:1.032-2.735),high sNRP-1 levels (HR=1.506,95%CI:1.354-4.043),lymph node metastasis (HR=1.902,95%CI:1.432-4.963),and TNM stage Ⅲ (HR=1.603,95%CI:1.241-4.035) were independent risk factors for postoperative recurrence in breast cancer patients (P<0.05).The 3-year OS rate in the high sCLU group was lower than that in the low sCLU group (62.39% vs. 87.07%,Log-rankχ ²=19.330,P<0.05),and the 3-year OS rate in the high sNRP-1 group was also lower than that in the low sNRP-1 group (60.87% vs. 88.14%,Log-rankχ ²=23.331,P<0.05).Multivariate Cox regression analysis further demonstrated that high sCLU levels (HR=1.805,95%CI:1.532-4.841),high sNRP-1 levels (HR=1.653,95%CI:1.214-4.217),lymph node metastasis (HR=1.824,95%CI:1.702-5.362),and postoperative recurrence (HR=2.241,95%CI:1.893-6.382) were independent risk factors affecting patient prognosis (P<0.05). Conclusion Elevated serum levels of sCLU and sNRP-1 in breast cancer patients are associated with postoperative recurrence and poor prognosis after modified radical mastectomy,and may serve as potential biomarkers for predicting postoperative recurrence and survival outcomes.

关键词

乳腺癌 / 改良根治术 / 局部复发 / 预后 / 分泌型丛生蛋白 / 可溶性神经纤毛蛋白1

Key words

breast cancer / modified radical mastectomy / local recurrence / prognosis / secretory clusterin / soluble neuropilin-1

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基金资助

重庆市黔江区科技计划项目(黔科计2025099)