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Series GSE130160 Query DataSets for GSE130160
Status Public on Sep 12, 2019
Title Patient-derived xenograft models of non-small cell lung cancer for evaluating targeted drug sensitivity and resistance
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Background: Patient-derived xenograft (PDX) models are a useful tool in cancer biology research. However, the number of lung cancer PDXs is limited
Results: In the present study, we successfully established ten PDXs, including three adenocarcinoma (AD), six squamous cell carcinoma (SQ) and one large cell carcinoma (LA), from 30 patients with non-small cell lung cancer (NSCLC) (18 AD, 10 SQ, and 2 LA), mainly in SHO mice (Crlj:SHO-PrkdcscidHrhr). Histology of SQ, advanced clinical stage (III-IV), status of lymph node metastasis (N2-3), and maximum standardized uptake value (SUVmax) ≧10 when evaluated using a delayed 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scan, was associated with successful PDX establishment. Histological analyses revealed that PDXs showed a histology similar to that of patients’ surgically resected tumors (SRTs), while components of the microenvironments were replaced with murine cells after several passages. Next generation sequencing and microarray analyses demonstrated that after 2 to 6 passages, PDXs preserved the majority of the somatic mutations and mRNA expressions of the corresponding SRTs. Two out of three PDXs with AD histology had EGFR mutations (L858R or exon19 deletion) and were sensitive to EGFR tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and osimertinib. Furthermore, in one of the two PDXs with an EGFR mutation, osimertinib resistance was induced that was associated with epithelial-to-mesenchymal transition.
Conclusions: This study presented ten serially transplantable PDXs of NSCLC in SHO mice and demonstrated the use of PDXs with an EGFR mutation for analyses of EGFR-TKI resistance.
Overall design Lung cancer mRNA profiles of from six paired samples of PDXs and SRTs were generated by deep sequencing using Illumina HiSeq 2500.
Contributor(s) Kita K, Takahashi H, Yano S
Citation(s) 31432603
Submission date Apr 22, 2019
Last update date Sep 12, 2019
Contact name Hiro Takahashi
Organization name Kanazawa University
Street address Kakuma-machi
City Kanazawa
State/province Ishikawa
ZIP/Postal code 920-1192
Country Japan
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (12)
GSM3733257 PDX #02
GSM3733258 PDX #05
GSM3733259 PDX #07
BioProject PRJNA534119
SRA SRP193382

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Supplementary file Size Download File type/resource
GSE130160_TR_5253.genes.fpkm_table3.txt.gz 3.4 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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