Abstract | BACKGROUND:
Colorectal cancer (CRC) is a common gastrointestinal tumor with subtle, often undetectable early symptoms, which means that upon diagnosis, patients often present in the middle or late stages of disease. Therefore, the need for an effective biomarker for the early diagnosis and development of novel therapeutic targets is urgent to prolong patient survival time and reduce mortality. METHODS: Twenty mice were randomly divided into patient-derived xenograft (PDX) model ( transplantation of fresh CRC tumor samples) and control groups (10 mice in each group). All the animals were euthanized using isoflurane at the end of the experiment. Gas chromatography-mass spectrometry (GC-MS)-based metabolomic profiling was performed to investigate the differential metabolites in the serum, and publicly available gene expression data (GSE106582) were analyzed to determine dysregulated metabolic pathways. Joint pathway analysis was used to identify potential metabolic targets. Immunohistochemistry analysis was performed to confirm the presence of the identified targets at the protein level. RESULTS: CONCLUSIONS: By combining GC-MS-based metabolomics profiling with a PDX model of CRC our study successfully identified potential diagnostic circulating metabolites. Dysregulated amino acid metabolism was found to be a significant feature of CRC. The amino acid transporters, SLC7A5 and SLC1A5, were identified as potential metabolic therapeutic targets. This study furthers the understanding of the metabolic processes involved in CRC.
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Authors | Juan Ni, Yang Chen, Ningning Li, Diandian Sun, Haixing Ju, Zhongjian Chen |
Journal | Translational cancer research
(Transl Cancer Res)
Vol. 10
Issue 4
Pg. 1813-1825
(Apr 2021)
ISSN: 2219-6803 [Electronic] China |
PMID | 35116504
(Publication Type: Journal Article)
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Copyright | 2021 Translational Cancer Research. All rights reserved. |