GSE183477
RNAseq analysis of treatment-resistant and sensitive breast cancer patient-derived organoids with paclitaxel treatments
Huntsman Cancer Institute (HCI)-001 patient-derived organoids (PDOs) and HCI-002 PDOs obtained from Huntsman Cancer Institute, University of Utah (Nat Med. 2011 Oct 23;17(11):1514-20). Purpose: The goals of this study is to identify molecular pathways and genes that are involved in the treatment responsiveness of breast cancer PDOs. Methods: mRNA profiles of HCI-001 and HCI-002 PDOs were generated by Illumina NovaSeq 6000 platform for paired-end sequencing, 150-bp read length, for about 20 million raw reads per sample. RNA sequencing FASTQ files were processed with HISAT2 aligner in default mode with the Ensembl human transcriptome annotation (Build version GRCh38 and transcript annotation GRCh38.89). Differential gene expression analysis was performed using DESeq2 software. Enrichment analysis was performed using ClusterProfiler software. Results: We mapped about 20 million sequence reads per sample to the human genome (build HG38) in the RNAs of HCI-001 and HCI-002 PDOs treated with paclitaxel or vehicle. We used a minimum expression cut-off of 1 FPKM in order to exclude low-levels genes and the RNA-seq data confirmed the difference expression of 67 known apoptosis-regulatory genes in treatment-sensitive PDOs (HCI-002) compare to treatment-resistant PDOs (HCI-001). Conclusions: This study identified apoptosis-regulatory genes that are differentially induced or represeed in treatment-sensitive PDOs (HCI-002) or treatment-resistant PDOs (HCI-001). Overall design: mRNA profiles of HCI-001 PDOs and HCI-002 PDOs treated with pacliaxel (20 uM) or vehicle for 48 hours