奥沙利铂
结直肠癌
类有机物
福克斯
抗药性
医学
癌症研究
肿瘤科
生物
内科学
癌症
生物信息学
遗传学
作者
Guanglong Chen,Ting Gong,Zhe Wang,Zeyu Wang,Xiao-Lin Lin,Sunrui Chen,Chu Sun,Weijie Zhao,Ye Kong,Huihan Ai,Hang Yang,Yusheng Liu,Fangyan Wu,Jiawei Kang,Shasha Zhao,Xiuying Xiao,Jing Ping Sun,Aina He,Zhi Li
标识
DOI:10.1007/s13402-022-00705-5
摘要
PurposeOxaliplatin-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.MethodsHere, 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).ResultsWe 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).ConclusionWe generated an oxaliplatin-resistant CRC organoid model that was employed to provide potential therapeutic targets for treating CRC patients exhibiting oxaliplatin-resistance.
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