Longitudinal genomic profiling using liquid biopsies in metastatic nonsquamous NSCLC following first line immunotherapy
Abstract Tumor genomic profiling is often limited to one or two timepoints due to the invasiveness of tissue biopsies, but longitudinal profiling may provide deeper clinical insights. Using ctDNA data from IMpower150 study, we examined genetic changes in metastatic non-squamous NSCLC post-first-line...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-024-00797-2 |
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| author | Haolun Ding Min Yuan Yaning Yang Xu Steven Xu |
| author_facet | Haolun Ding Min Yuan Yaning Yang Xu Steven Xu |
| author_sort | Haolun Ding |
| collection | DOAJ |
| description | Abstract Tumor genomic profiling is often limited to one or two timepoints due to the invasiveness of tissue biopsies, but longitudinal profiling may provide deeper clinical insights. Using ctDNA data from IMpower150 study, we examined genetic changes in metastatic non-squamous NSCLC post-first-line immunotherapy. Mutations were most frequently detected in TP53, KRAS, SPTA1, FAT3, and LRP1B at baseline and during treatment. Mutation levels rose prior to radiographic progression in most progressing patients, with specific mutations (SPTA1, STK11, KEAP1, SMARCA4, TBX3, CDH2, and MLL3) significantly enriched in those with progression or nondurable response. However, ctDNA’s role in detecting hyperprogression and pseudoprogression remains uncertain. STK11, SMARCA4, KRAS, SLT2, and KEAP1 mutations showed the strongest correlation with poorer overall survival, while SMARCA4, STK11, SPTA1, TBX3, and KEAP1 mutations correlated with shorter progression-free survival. Overall, longitudinal liquid biopsy profiling provided valuable insights into lung cancer biology post-immunotherapy, potentially guiding personalized therapies and future drug development. |
| format | Article |
| id | doaj-art-12c04849db9349828da1a623c13db78f |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-12c04849db9349828da1a623c13db78f2025-01-12T12:06:22ZengNature Portfolionpj Precision Oncology2397-768X2025-01-01911810.1038/s41698-024-00797-2Longitudinal genomic profiling using liquid biopsies in metastatic nonsquamous NSCLC following first line immunotherapyHaolun Ding0Min Yuan1Yaning Yang2Xu Steven Xu3Department of Statistics and Finance, School of Management, University of Science and Technology of ChinaDepartment of Health Data Science, Anhui Medical UniversityDepartment of Statistics and Finance, School of Management, University of Science and Technology of ChinaClinical Pharmacology and Quantitative Science, Genmab IncAbstract Tumor genomic profiling is often limited to one or two timepoints due to the invasiveness of tissue biopsies, but longitudinal profiling may provide deeper clinical insights. Using ctDNA data from IMpower150 study, we examined genetic changes in metastatic non-squamous NSCLC post-first-line immunotherapy. Mutations were most frequently detected in TP53, KRAS, SPTA1, FAT3, and LRP1B at baseline and during treatment. Mutation levels rose prior to radiographic progression in most progressing patients, with specific mutations (SPTA1, STK11, KEAP1, SMARCA4, TBX3, CDH2, and MLL3) significantly enriched in those with progression or nondurable response. However, ctDNA’s role in detecting hyperprogression and pseudoprogression remains uncertain. STK11, SMARCA4, KRAS, SLT2, and KEAP1 mutations showed the strongest correlation with poorer overall survival, while SMARCA4, STK11, SPTA1, TBX3, and KEAP1 mutations correlated with shorter progression-free survival. Overall, longitudinal liquid biopsy profiling provided valuable insights into lung cancer biology post-immunotherapy, potentially guiding personalized therapies and future drug development.https://doi.org/10.1038/s41698-024-00797-2 |
| spellingShingle | Haolun Ding Min Yuan Yaning Yang Xu Steven Xu Longitudinal genomic profiling using liquid biopsies in metastatic nonsquamous NSCLC following first line immunotherapy npj Precision Oncology |
| title | Longitudinal genomic profiling using liquid biopsies in metastatic nonsquamous NSCLC following first line immunotherapy |
| title_full | Longitudinal genomic profiling using liquid biopsies in metastatic nonsquamous NSCLC following first line immunotherapy |
| title_fullStr | Longitudinal genomic profiling using liquid biopsies in metastatic nonsquamous NSCLC following first line immunotherapy |
| title_full_unstemmed | Longitudinal genomic profiling using liquid biopsies in metastatic nonsquamous NSCLC following first line immunotherapy |
| title_short | Longitudinal genomic profiling using liquid biopsies in metastatic nonsquamous NSCLC following first line immunotherapy |
| title_sort | longitudinal genomic profiling using liquid biopsies in metastatic nonsquamous nsclc following first line immunotherapy |
| url | https://doi.org/10.1038/s41698-024-00797-2 |
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