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Integration of Metabolomics and Transcriptomics To Reveal Metabolic Characteristics and Key Targets Associated with Cisplatin Resistance in Nonsmall Cell Lung Cancer
journal contribution
posted on 2019-08-16, 15:45 authored by Yuhuan Shi, Yuanyuan Wang, Wanying Huang, Yang Wang, Rong Wang, Yongfang YuanContinuous exposure
to cisplatin can induce drug resistance to
limit efficacy; however, the underlying mechanisms correlated with
cisplatin resistance are still unclear. Drug-sensitive A549 cells
and cisplatin-resistant A549/DDP cells were used to explore the potential
metabolic pathways and key targets associated with cisplatin resistance
by integrating untargeted metabolomics with transcriptomics. Data
are available via ProteomeXchange with identifier PXD013265. The results
of comprehensive analyses showed that 19 metabolites were significantly
changed in A549/DDP versus A549 cells, and some pathways had a close
relationship with cisplatin resistance, such as the biosynthesis of
aminoacyl-tRNA, glycerophospholipid metabolism, and glutathione metabolism.
Moreover, transcriptomics analysis showed that the glutathione metabolism
was also obviously affected in A549/DDP, which indicated that the
glutathione metabolism played an important role in the process of
drug resistance. Meanwhile, transcriptomics analysis suggested the
four enzymes related to glutathione metabolismCD13, GPX4,
RRM2B, and OPLAHas potential targets of cisplatin resistance
in nonsmall cell lung cancer. Further studies identified the overexpression
of these four enzymes in A549/DDP. The elucidation of mechanism and
discovery of new potential targets may help us have a better understanding
of cisplatin resistance.