CD4+和CD8+T细胞凋亡对乳腺癌保乳术后放疗不良反应的预测价值OA
Predictive value of CD4+and CD8+T lymphocyte apoptosis for radiation-induced adverse effects following breast-conserving surgery
目的 探讨CD4+和CD8+T淋巴细胞凋亡水平对乳腺癌保乳术后大分割放疗(HFRT)引发的乳房相关放射性不良反应的预测价值.方法 收集 2020 年 7 月至 2021 年 9 月在唐山市人民医院接受保乳术后瘤床同步补量HFRT的 72 例患者的临床数据.根据通用不良事件术语标准评估乳房相关放射性不良反应的严重程度.采集新鲜血液样本,并对样本进行 8Gy X线照射处理.使用流式细胞仪分析CD4+和CD8+T淋巴细胞的凋亡情况.同时,从放疗前后的乳腺组织中提取样本进行免疫组化分析,评估CD4+和CD8+T细胞的浸润情况.Cox回归分析患者不良反应程度的影响因素.通过Spearman相关分析评估淋巴细胞凋亡与不良反应等级的关系.采用受试者工作特征曲线(ROC)分析CD4+和CD8+T细胞凋亡对预测乳房相关放射性不良反应的价值.此外,比较不同淋巴细胞凋亡水平患者的 2年累积发生率,并利用多因素回归分析调整潜在的混杂因素.结果 72 例患者至少随访 2 年,≤1 级和≥2 级乳房相关放射性不良反应事件分别为 51 例(70.8%)和 21 例(29.2%).不良反应≤1 级患者糖尿病史占比、T2 分期占比低于≥2 级患者,CD8+T 细胞放疗所致淋巴细胞凋亡(RILA)水平、CD4+T细胞RILA水平高于≥2 级患者,差异有统计学意义(P<0.05).Cox回归结果显示,T分期(OR=11.143,95%CI:1.703~72.908)、CD8+T细胞RILA水平(OR=0.273,95%CI:0.157~0.473)、CD4+T细胞RILA水平(OR=0.211,95%CI:0.103~0.431)是患者不良反应程度的独立影响因素(P<0.05).ROC曲线分析显示,CD8+T细胞RILA预测≥2 级乳房相关放射性不良反应的曲线下面积(AUC)为 0.947(95%CI:0.806~1.000),CD4+T RILA的AUC为 0.824(95%CI:0.654~1.000),差异有统计学意义(P<0.05).Spearman相关分析显示,CD8+和CD4+T RILA水平与乳房相关放射性不良反应严重程度呈负相关(r=-0.831、-0.704,P<0.01).CD8+T细胞RILA≤11.13%的患者显著高于CD8+T细胞RILA>11.13%的患者(11.90%),差异具有统计学意义(P<0.05).CD4+T细胞RILA≤7.36%的患者 2 年累积发生率为39.39%,高于CD4+T细胞RILA>7.36%的患者(20.51%),差异无统计学意义(P>0.05).免疫组化结果显示,放疗后CD8+T细胞的浸润增加,并与放射性不良反应的严重程度相关.结论 放疗所致CD8+T淋巴细胞凋亡及其相关的免疫细胞浸润和基因表达变化对预测乳腺癌保乳术后大分割放疗乳房相关放射性不良反应具有重要价值.通过整合CD8+T细胞凋亡、免疫组化数据,可进一步提升对放疗相关风险的预测能力,为个体化放疗和预防策略的制定提供参考.
Objective This study aims to explore the potential of CD4+and CD8+T lymphocyte apoptosis as biomarkers for predicting radiation-induced adverse effects in the breast following breast-conserving surgery(BCS)and subsequent simultaneous integrated boost hypofractionated radiotherapy(HFRT)for breast cancer.Methods Clinical data from 72 patients who underwent BCS followed by concurrent boost HFRT at Tangshan People's Hospital from July 2020 to September 2021 were collected.The severity of radiation-induced adverse effects in the breast was assessed according to common terminology criteria for adverse events.Fresh blood samples were collected,exposed to 8Gy X-ray irradiation,and analyzed using flow cytometry to evaluate CD4+and CD8+T lymphocyte apoptosis.Additionally,pre-and post-radiotherapy breast tissue samples were extracted for immunohistochemical analysis to assess CD4+and CD8+T cell infiltration.Cox regression was used to analyze the factors influencing the degree of adverse reactions.Spearman correlation analysis was used to evaluate the relationship between lymphocyte apoptosis and the severity of adverse effects.Receiver operating characteristic(ROC)curve analysis was employed to assess the predictive value of CD4+and CD8+T lymphocyte apoptosis for breast-related radiation adverse effects.The 2-year cumulative incidence rates of different lymphocyte apoptosis levels were compared,and multivariate regression analysis was used to adjust for potential confounding factors.Results A total of seventy two patients were followed up for at least 2 years.There were fifty one patients(70.8%)with grade≤1 and twenty one patients(29.2%)with grade≥2 breast related adverse reactions,respectively.The proportion of diabetes history and T2 stage in patients with≤grade 1 was higher than that in patients with≥grade 2,and the radiation induced lymphocyte apoptosis(RILA)level of CD8+T cell and CD4+T cell were higher than that in patients with≥grade 2,with statistical significance(P<0.05).Cox regression results showed that T stage(OR=11.143,95%CI:1.703-72.908),CD8+T cell RILA level(OR=0.273,95%CI:0.157-0.473)and CD4+T cell levels(OR=0.211,95%CI:0.103-0.431)were independent influencing factors for the degree of adverse reactions(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of CD8+T cell RILA to predict grade 2 breast related adverse radiation reactions was 0.947(95%CI:0.806-1.000),and the AUC of CD4+T cell RILA was 0.824(95%CI:0.654-1.000).,the difference was statistically significant(P<0.05).Conclusions CD8+T lymphocyte apoptosis,along with associated immune cell infiltration and gene expression changes,holds significant predictive value for radiation-induced adverse effects in the breast following BCS and SBRT for breast cancer.Integrating CD8+T cell apoptosis and immunohistochemical data can further enhance the predictive capability for radiotherapy-related risks and provide reference for personalized radiotherapy and prevention strategies.
王建廷;邵瑞雨;王晶;李娜;熊伟;王晓红
063001 河北 唐山,唐山市人民医院 放化六科063001 河北 唐山,唐山市人民医院 放化六科063001 河北 唐山,唐山市人民医院 乳外四科063001 河北 唐山,唐山市人民医院 放化六科063001 河北 唐山,唐山市人民医院 放化七科063001 河北 唐山,唐山市人民医院 放化六科
乳腺癌保乳术大分割放疗CD4+T细胞凋亡CD8+T细胞凋亡不良反应
Breast cancerBreast-conserving surgeryHypofractionated radiotherapyCD4+T cell apoptosisCD8+T cell apoptosisAdverse reaction
《中国肿瘤外科杂志》 2026 (1)
57-63,7
河北省医学科学研究课题计划资助(20211663)
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