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

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...

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Main Authors: Narumol Trachu, Thanyanan Reungwetwattana, Jennis Meanwatthana, Chonlaphat Sukasem, Teerapat Majam, Wacharapol Saengsiwaritt, Jiraphun Jittikoon, Wanvisa Udomsinprasert
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Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-77935-0
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author Narumol Trachu
Thanyanan Reungwetwattana
Jennis Meanwatthana
Chonlaphat Sukasem
Teerapat Majam
Wacharapol Saengsiwaritt
Jiraphun Jittikoon
Wanvisa Udomsinprasert
author_facet Narumol Trachu
Thanyanan Reungwetwattana
Jennis Meanwatthana
Chonlaphat Sukasem
Teerapat Majam
Wacharapol Saengsiwaritt
Jiraphun Jittikoon
Wanvisa Udomsinprasert
author_sort Narumol Trachu
collection DOAJ
description 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.
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spelling doaj-art-31980476529c47eebb660187cb7ab4492025-08-20T02:13:55ZengNature PortfolioScientific Reports2045-23222024-11-0114111110.1038/s41598-024-77935-0Leukocytes telomere length as a biomarker of adverse drug reactions induced by Osimertinib in advanced non-small cell lung cancerNarumol Trachu0Thanyanan Reungwetwattana1Jennis Meanwatthana2Chonlaphat Sukasem3Teerapat Majam4Wacharapol Saengsiwaritt5Jiraphun Jittikoon6Wanvisa Udomsinprasert7Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityDivision of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityDepartment of Pharmacy, Faculty of Pharmacy, Mahidol UniversityDivision of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversitySchool of Pharmacy, Walailak UniversityDepartment of Biochemistry, Faculty of Pharmacy, Mahidol UniversityDepartment of Biochemistry, Faculty of Pharmacy, Mahidol UniversityDepartment of Biochemistry, Faculty of Pharmacy, Mahidol UniversityAbstract 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.https://doi.org/10.1038/s41598-024-77935-0Telomere lengthNon-small cell lung cancerOsimertinibOsimertinib-induced adverse drug reactionsBiomarker
spellingShingle Narumol Trachu
Thanyanan Reungwetwattana
Jennis Meanwatthana
Chonlaphat Sukasem
Teerapat Majam
Wacharapol Saengsiwaritt
Jiraphun Jittikoon
Wanvisa Udomsinprasert
Leukocytes telomere length as a biomarker of adverse drug reactions induced by Osimertinib in advanced non-small cell lung cancer
Scientific Reports
Telomere length
Non-small cell lung cancer
Osimertinib
Osimertinib-induced adverse drug reactions
Biomarker
title Leukocytes telomere length as a biomarker of adverse drug reactions induced by Osimertinib in advanced non-small cell lung cancer
title_full Leukocytes telomere length as a biomarker of adverse drug reactions induced by Osimertinib in advanced non-small cell lung cancer
title_fullStr Leukocytes telomere length as a biomarker of adverse drug reactions induced by Osimertinib in advanced non-small cell lung cancer
title_full_unstemmed Leukocytes telomere length as a biomarker of adverse drug reactions induced by Osimertinib in advanced non-small cell lung cancer
title_short Leukocytes telomere length as a biomarker of adverse drug reactions induced by Osimertinib in advanced non-small cell lung cancer
title_sort leukocytes telomere length as a biomarker of adverse drug reactions induced by osimertinib in advanced non small cell lung cancer
topic Telomere length
Non-small cell lung cancer
Osimertinib
Osimertinib-induced adverse drug reactions
Biomarker
url https://doi.org/10.1038/s41598-024-77935-0
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