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Colorectal cancer organoid models uncover oxaliplatin-resistant mechanisms at single cell resolution
- Source :
- Cellular Oncology.
- Publication Year :
- 2022
- Publisher :
- Springer Science and Business Media LLC, 2022.
-
Abstract
- Oxaliplatin-based chemotherapy is a standard treatment for advanced colorectal cancer (CRC) patients. However, chemoresistance-induced resistance is an essential cause for mortality. Therefore, it is necessary to study the mechanism of drug resistance in CRC.Here, we established two strains of patient-derived organoids (PDOs) selected from oxaliplatin-resistant and treatment-naïve CRC patients. To dissect the drug-resistant mechanisms, these CRC-PDOs were subjected to single-cell RNA sequencing (scRNA-Seq).We found that the drug sensitivity test outcome from these organoids subjected to oxaliplatin and 5-FU exposure was consistent with the clinic readout. CRC-PDOs well recapitulated the morphology and histology of their parental biopsies based on HE and IHC staining of pathological biomarkers. The scRNA-Seq data filtered drug-resistant cell populations and related signaling pathways (e.g. oxidative phosphorylation and ATP metabolic process). The data also revealed several putative drug resistant-driven genes (STMN1, VEGFA and NDRG1) and transcription factors (E2F1, BRCA1, MYBL2, CDX2 and CDX1).We generated an oxaliplatin-resistant CRC organoid model that was employed to provide potential therapeutic targets for treating CRC patients exhibiting oxaliplatin-resistance.
Details
- ISSN :
- 22113436 and 22113428
- Database :
- OpenAIRE
- Journal :
- Cellular Oncology
- Accession number :
- edsair.doi.dedup.....77c096116597d930963cf21b6a83978e