In:
Journal of Translational Medicine, Springer Science and Business Media LLC, Vol. 17, No. 1 ( 2019-12)
Abstract:
Pemetrexed combined with platinum complexes can be used as first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC), however, the efficacy and safety is varying from individuals. There is a need to better understand the genetic variations associated with platinum response. Materials and Methods We performed next-generation sequencing (NGS) based on BGI Oseq-ctDNA panel to analyze 98 longitudinal plasma samples from 32 lung adenocarcinoma patients during platinum-based chemotherapy, and a bioinformatic pipeline was developed to detect point mutations. Results We found that mutation burden was decreased after chemotherapy, which reflected chemotherapy sensitivity, especially the frequency of C 〉 G and C 〉 A substitutions. Moreover, neoplastic cells carrying a specific set of somatic mutations, such as EGFR(L858R) , KRAS (p.G12C) were obviously correlated with platinum treatment. In addition, the MAPK pathway was found to have a pivotal role in NSCLC and platinum based response. Finally, we found that smokers benefit less from platinum-based chemotherapy. Conclusions Collectively, this work described the dynamic changes of ctDNA mutation status during platinum-based treatment, which may contribute to advanced lung adenocarcinoma patients stratification and precision treatment.
Type of Medium:
Online Resource
ISSN:
1479-5876
DOI:
10.1186/s12967-019-2087-9
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2019
detail.hit.zdb_id:
2118570-0
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