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白细胞端粒长度作为奥希替尼诱导晚期非小细胞肺癌不良药物反应的生物标志物。

Leukocytes telomere length as a biomarker of adverse drug reactions induced by Osimertinib in advanced non-small cell lung cancer.

机构信息

Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

出版信息

Sci Rep. 2024 Nov 3;14(1):26543. doi: 10.1038/s41598-024-77935-0.

Abstract

This study aimed to measure relative telomere length (RTL) in blood leukocytes of advanced-stage NSCLC patients either with or without Osimertinib-induced ADRs and determine whether RTL could serve as a biomarker of Osimertinib-induced ADRs. Blood leukocytes RTL were measured in 63 advanced-stage NSCLC patients and 62 age-matched healthy controls using real-time polymerase chain reaction. In patients with advanced-stage NSCLC, RTL was significantly shorter than that in healthy controls (P < 0.001). Compared to patients without ADRs and those with mild/moderate ADRs, patients with severe ADRs exhibited significantly decreased RTL (P < 0.001, P < 0.001, respectively). ROC curve analysis uncovered a diagnostic value of RTL as a biomarker of Osimertinib-induced ADRs (AUC = 1.000, P < 0.001). Kaplan-Meier analysis revealed a significant association between shorter RTL and increased cumulative incidence of Osimertinib-induced ADRs in patients with advanced-stage NSCLC (P < 0.001). Shorter RTL in blood leukocytes would reflect the occurrence of Osimertinib-induced ADRs and might emerge as a promising biomarker for identifying advanced-stage NSCLC patients who are at risk of experiencing Osimertinib-induced ADRs, particularly those with severe ADRs.

摘要

本研究旨在测量晚期 NSCLC 患者(有无奥希替尼诱导的不良反应)血液白细胞中的相对端粒长度(RTL),并确定 RTL 是否可作为奥希替尼诱导的不良反应的生物标志物。采用实时聚合酶链反应(PCR)检测 63 例晚期 NSCLC 患者和 62 名年龄匹配的健康对照者的血液白细胞 RTL。与健康对照组相比,晚期 NSCLC 患者的 RTL 明显缩短(P < 0.001)。与无不良反应和轻度/中度不良反应的患者相比,严重不良反应的患者 RTL 明显降低(P < 0.001,P < 0.001)。ROC 曲线分析显示 RTL 作为奥希替尼诱导的不良反应生物标志物具有诊断价值(AUC = 1.000,P < 0.001)。Kaplan-Meier 分析显示,晚期 NSCLC 患者中 RTL 较短与奥希替尼诱导的不良反应累积发生率增加之间存在显著相关性(P < 0.001)。血液白细胞 RTL 较短反映了奥希替尼诱导的不良反应的发生,可能成为识别有发生奥希替尼诱导的不良反应风险的晚期 NSCLC 患者的有前途的生物标志物,尤其是那些有严重不良反应的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/034f/11532503/9e4a5899f88b/41598_2024_77935_Fig1_HTML.jpg

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