血清SGK1、14,15-DHET、MLR对Her2<sup>+</sup>转移性乳腺癌患者化疗相关心脏毒性的评估价值-东南大学学报医学版

血清SGK1、14,15-DHET、MLR对Her2⁺转移性乳腺癌患者化疗相关心脏毒性的评估价值

单位：1. 沧州市人民医院乳腺外科, 河北沧州 061001;
2. 沧州市人民医院肿瘤内科, 河北沧州 061001;
3. 沧州市人民医院血液科, 河北沧州 061001

关键词：人类表皮生长因子受体2 转移性乳腺癌血清/糖皮质激素调节激酶1 14 15-二羟基二十碳三烯酸单核细胞/淋巴细胞比值心脏毒性预测

分类号：R737.9

出版年·卷·期（页码）：2026·45·第四期（621-629）

摘要：

目的:探究血清/糖皮质激素调节激酶1(SGK1)、14,15-二羟基二十碳三烯酸(14,15-DHET)及单核细胞/淋巴细胞比值(MLR)对人类表皮生长因子受体2阳性(Her2⁺)转移性乳腺癌(mBC)患者化疗相关心脏毒性的评估价值。方法:连续选取2020年9月至2024年4月沧州市人民医院收治的165例Her2⁺ mBC患者,纳入Her2⁺组,根据化疗后是否出现心脏毒性分为毒性组(n=41)和无毒性组(n=124)。另选取165例健康志愿者作为正常对照(NC)组。检测血清SGK1、14,15-DHET和MLR水平;构建多因素Logistic回归模型分析独立危险因素;受试者工作特征(ROC)曲线评估血清SGK1、14,15-DHET和MLR水平对心脏毒性的预测效能;采用1 000次Bootstrap法进行内部验证,以Hosmer-Lemeshow检验评价模型拟合度。决策曲线分析与临床影响曲线评估模型在临床决策中的实际获益。结果:NC组血清SGK1、14,15-DHET和MLR水平低于Her2⁺组(P<0.05);与无毒性组相比,毒性组血清肌酸激酶同工酶、SGK1、14,15-DHET和MLR水平显著升高(P<0.05);SGK1、14,15-DHET和MLR升高是影响心脏毒性的独立危险因素(P＜0.05);血清SGK1、14,15-DHET和MLR水平联合预测心脏毒性的ROC曲线下面积为0.961,显著高于单一指标预测的0.805、0.818、0.837(P＜0.05),且具有较低的过拟合风险和良好的泛化能力。该联合模型(SGK1/14,15-DHET/MLR)不仅在0.02~0.97的宽泛阈值范围内持续保持更优的净获益,且在高风险阈值(>0.5)处,其预测阳性数量与真实发病情况基本一致。结论:Her2⁺ mBC患者血清SGK1、14,15-DHET和MLR水平升高是化疗相关心脏毒性的关键生物标志物,三者联合对心脏毒性的早期预测具有较高的评估价值。

Objective: To investigate the predictive value of serum serum/glucocorticoid-regulated kinase 1(SGK1), 14,15-dihydroxyeicosatrienoic acid(14,15-DHET), and monocyte-to-lymphocyte ratio(MLR) for chemotherapy-related cardiotoxicity in patients with human epidermal growth factor receptor 2-positive(Her2⁺) metastatic breast cancer(mBC).Methods: A total of 165 consecutive patients with Her2⁺ mBC admitted to Cangzhou People's Hospital between September 2020 and April 2024 were enrolled as the Her2⁺ cohort. Based on the occurrence of post-chemotherapy cardiotoxicity, patients were subdivided into a cardiotoxicity group(n=41) and a non-cardiotoxicity group(n=124). An additional 165 healthy volunteers were recruited as the normal control(NC) group. Serum levels of SGK1 and 14,15-DHET, as well as MLR, were detected and compared across groups. Multivariate Logistic regression was constructed to identify independent risk factors for cardiotoxicity. Receiver operating characteristic(ROC) curve analysis was performed to assess the predictive performance of SGK1, 14,15-DHET, and MLR alone and in combination. Internal validation was implemented via 1 000 bootstrap resamples, and the Hosmer-Lemeshow test was applied to evaluate model calibration. Decision curve analysis(DCA) and clinical impact curves were further generated to quantify the net clinical benefit of the predictive model. Results: Serum SGK1, 14,15-DHET, and MLR levels were significantly lower in the NC group relative to the Her2⁺ cohort(all P<0.05). Compared with the non-cardiotoxicity subgroup, patients who developed cardiotoxicity exhibited markedly elevated serum creatine kinase-MB, SGK1, 14,15-DHET, and MLR levels(all P<0.05). Multivariate analysis confirmed that increased SGK1, 14,15-DHET, and MLR were independent risk factors for chemotherapy-related cardiotoxicity(all P<0.05). The combined panel of SGK1, 14,15-DHET, and MLR yielded an area under the curve(AUC) of 0.961 for predicting cardiotoxicity, which was significantly higher than the AUC values of individual biomarkers(0.805, 0.818, and 0.837, respectively; all P<0.05). The combined model showed low overfitting risk and favorable generalizability. DCA demonstrated sustained superior net clinical benefit across a broad risk threshold range of 0.02-0.97. At high-risk thresholds(>0.5), the number of predicted positive cases closely matched the actual incidence of cardiotoxicity. Conclusion: Elevated serum SGK1, 14,15-DHET, and MLR are key circulating biomarkers indicative of chemotherapy-related cardiotoxicity in patients with Her2⁺ mBC. The combined detection of these three indicators provides robust early predictive performance for chemotherapy-induced cardiac injury in this patient population.

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