Dataset Information
A novel patient-derived organoids-based xenografts model for preclinical drug response testing in patients with colorectal liver metastases.
Ontology highlight
ABSTRACT: Backgrounds
Cancer-related mortality in patients with colorectal cancer (CRC) is predominantly caused by development of colorectal liver metastases (CLMs). How to screen the sensitive chemotherapy and targeted therapy is the key element to improve the prognosis of CLMs patients. The study aims to develop patient-derived organoids-based xenografted liver metastases (PDOX-LM) model of CRC, to recapitulate the clinical drug response.Methods
We transplanted human CRC primary tumor derived organoids in murine spleen to obtain xenografted liver metastases in murine liver. Immunohistochemistry (IHC) staining, whole-exome and RNA sequencing, and drug response testing were utilized to identify the homogeneity in biological and genetic characteristics, and drug response between the PDOX-LM models and donor liver metastases.Results
We successfully established PDOX-LM models from patients with CLMs. IHC staining showed that positive expression of CEA, Ki67, VEGF, FGFR2 in donor liver metastases were also well preserved in matched xenografted liver metastases. Whole-exon sequencing and transcriptome analysis showed that both xenografted and donor liver metastases were highly concordant in somatic variants (??0.90 frequency of concordance) and co-expression of driver genes (Pearson's correlation coefficient reach up to 0.99, P?=?0.001). Furthermore, drug response testing showed that the PDOX-LM models can closely recapitulated the clinical response to mFOLFOX6 regiments.Conclusions
This PDOX-LM model provides a more convenient and informative platform for preclinical testing of individual tumors by retaining the histologic and genetic features of donor liver metastases. This technology holds great promise to predict treatment sensitivity for patients with CLMs undergoing chemotherapy.
SUBMITTER: Jian M
PROVIDER: S-EPMC7291745 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
A novel patient-derived organoids-based xenografts model for preclinical drug response testing in patients with colorectal liver metastases.
Journal of translational medicine 20200612 1
<h4>Backgrounds</h4>Cancer-related mortality in patients with colorectal cancer (CRC) is predominantly caused by development of colorectal liver metastases (CLMs). How to screen the sensitive chemotherapy and targeted therapy is the key element to improve the prognosis of CLMs patients. The study aims to develop patient-derived organoids-based xenografted liver metastases (PDOX-LM) model of CRC, to recapitulate the clinical drug response.<h4>Methods</h4>We transplanted human CRC primary tumor de ...[more]