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发育医学电子杂志  2025, Vol. 13 Issue (6): 462-468    DOI: 10.3969/j.issn.2095-5340.2025.06.009
  围产医学   论著 |新生儿 |
PI3K/AKT 信号轴关键因子对阈值期早产儿视网膜病变雷珠单抗治疗效果的预测价值
谢静  王秀先  左相荣  贾玉红  王丽芳
邢台市人民医院  眼科,河北  邢台054001 
Predictive value of PI3K/AKT signaling axis key factors on the therapeutic effect ofRanibizumab in threshold retinopathy of prematurity
Xie Jing, Wang Xiuxian, Zuo Xiangrong, et al
Department of Ophthalmology, Xingtai People's Hospital, Hebei, Xingtai 054001, China
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摘要 【摘要】 目的   探究磷脂酰肌醇 3- 激酶 / 蛋白激酶 B(phosphatidylinositol 3-kinase/protein kinase B , PI3K/AKT)信号轴关键因子对阈值期早产儿视网膜病变(retinopathy of prematurity,ROP)雷珠单抗治疗效果的预测价值。 方法  采用回顾性研究方法,选取 2020 年 6 月至 2023 年 8 月邢台市人民医院眼科收治的 154 例阈值期 ROP 早产儿为病例组,选取同期患有其他疾病但无 ROP 的 100 例早产儿作为对照组。采用 Western blotting 法检测并比较外周血单个核细胞中 PI3K、AKT 相对蛋白表达水平;根据治疗效果将其分为有效组(n=133)和无效组(n=21),采用单因素和多因素 Logistic 回归分析评价阈值期ROP 雷珠单抗治疗效果的影响因素。采用受试者工作特征(receiver operating characteristic,ROC)曲线分析外周血单个核细胞中 PI3K、AKT 相对蛋白表达水平对阈值期 ROP 及其雷珠单抗治疗效果的预测价值。采用 Spearman 法分析 PI3K/AKT 信号轴关键因子与阈值期 ROP 雷珠单抗治疗效果的相关性。结果  病例组早产儿外周血单个核细胞中 PI3K、AKT 相对蛋白表达水平高于对照组(PI3K:1.63 ±0.39与 0.56 ±0.12 ;AKT :1.47±0.35 与 0.68±0.16),差异均有统计学意义(P 值均 <0.001)。外周血单个核细胞中 PI3K 联合 AKT 预测阈值期 ROP 的曲线下面积(area under the curve,AUC)为 0.859(95%  CI :0.805~0.912),敏感度为 81.00%,特异度为 84.00%,联合检测体现出最优诊断价值。无效组治疗前眼底出血占比及 PI3K、AKT 相对蛋白表达水平均明显高于有效组,出生体质量低于有效组,差异均有统计学意义(P 值均 <0.05)。治疗前眼底出血、出生体质量低、PI3K 和 AKT 高表达是阈值期 ROP 雷珠单抗治疗无效的危险因素(P<0.05)。ROC 曲线分析结果显示,以 PI3K>1.76、AKT>1.53 为截断值时, 2 项指标联合预测阈值期 ROP 雷珠单抗治疗效果的 AUC 值为 0.909(95% CI :0.838~0.979),敏感度为80.95%,特异度为 86.47%。外周血单个核细胞中 PI3K、AKT 相对蛋白表达水平与阈值期 ROP 雷珠单抗治疗效果呈负相关(r 值为-0.431、-0.446,P<0.001)。 结论  PI3K/AKT 信号轴关键因子高表达与阈值期 ROP 雷珠单抗治疗效果欠佳显著相关,外周血单个核细胞中 PI3K、AKT 联合检测对于治疗效果预测有较高的临床价值。
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关键词:  磷脂酰肌醇 3- 激酶 / 蛋白激酶 B  阈值期早产儿视网膜病变  雷珠单抗  治疗效果  预测价值    
Abstract: 【Abstract 】 Objective    To explore the predictive value of phosphatidylinositol 3-kinase/protein kinaseB (PI3K/AKT) signaling axis key factors on the therapeutic e?ect of Ranibizumab in threshold retinopathy of prematurity (ROP).    Method    A retrospective study was conducted.  154 preterm infants with threshold ROP admitted to the Department oOphthalmology, Xingtai People's Hospital from June 2020 to August 2023 were selected as the case group, and 100 preterm infants with other diseases but no ROP during the same period were selected as the control group. The Western blotting method was used to detect and compare the relative expression levels of PI3K and AKT proteins in peripheral blood mononuclear cell (PBMC). Based on the treatment efficacy, the patients were divided into the e?ective group (n=133) and ine?ective group (n=21), Univariate and multivariate Logistic regression analyses were used to evaluate the in?uencing factors of the therapeutic e?ect of Ranibizumab on threshold ROP. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of PI3K and AKT relative expression in PBMC for threshold ROP and the therapeutic e?ect of Ranibizumab. Spearman method was used to analyze the correlation between key factors of the PI3K/AKT signaling axis and the therapeutic e?ect of Ranibizumab on threshold ROP.    Result    The relative expression levels of PI3K and AKT proteins in PBMC of the case group were higher than those of the control group (PI3K: 1.63 ±0.39vs 0.56±0.12; AKT: 1.47±0.35vs 0.68±0.16), and the di?erences were statistically signi?cant (all P<0.001). For the prediction of threshold ROP using combined PI3K and AKT in PBMC, the area under the curve (AUC) was 0.859 (95% CI: 0.805-0.912), with a sensitivity of 81.00%, and a speci?city of 84.00%, indicating that the combined detection exhibited the optimal diagnostic value. In the ine?ective treatment group, the proportion of fundus hemorrhage before treatment and the relative expression of PI3K and AKT proteins were signi?cantly higher than those in the e?ective treatment group, while the birth weight was lower than that in the e?ective treatment group, the di?erences were statistically signi?cant (all P<0.05). Fundus hemorrhage before treatment, low birth weight, high PI3K and AKT expression levels were identi?ed as the risk factors for poor response to Ranibizumab treatment for threshold ROP (all P<0.05). The results of ROC curve analysis showed that when the cut-o? values were set at PI3K>1.76 and AKT>1.53, the AUC of the combined detection of these two indicators for predicting the efficacy of Ranibizumab in treating threshold ROP was 0.909 (95% CI: 0.838-0.979), with a sensitivity of 80.95%, and a speci?city of 86.47%. Additionally, the relative expression levels of PI3K and AKT proteins in PBMC were negatively correlated with the therapeutic e?ect of Ranibizumab for threshold ROP (r values were -0.431, -0.446 respectively, all P<0.001).    Conclusion    High expression of PI3K/AKT signaling axis key factors is signi?cantly associated with poor therapeutic e?ect of Ranibizumab on threshold ROP. The combined detection of PI3K and AKT in PBMC has high clinical value in predicting the therapeutic e?ect.
Key words:  Phosphatidylinositol 3-kinase/protein kinase B    Threshold retinopathy of prematurity    Ranibizumab    Therapeutic e?ect    Predictive value
收稿日期:  2024-08-06                     发布日期:  2025-11-30     
基金资助: 邢台市重点研发计划自筹项目(2022ZC192)
通讯作者:  Xie Jing     E-mail:  461746732@qq.com
引用本文:    
谢静 王秀先 左相荣 贾玉红 王丽芳. PI3K/AKT 信号轴关键因子对阈值期早产儿视网膜病变雷珠单抗治疗效果的预测价值[J]. 发育医学电子杂志, 2025, 13(6): 462-468.
Xie Jing, Wang Xiuxian, Zuo Xiangrong, et al. Predictive value of PI3K/AKT signaling axis key factors on the therapeutic effect ofRanibizumab in threshold retinopathy of prematurity. Journal of Developmental Medicine(Electronic Version), 2025, 13(6): 462-468.
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