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Series GSE147864 Query DataSets for GSE147864
Status Public on Feb 05, 2021
Title The Molecular Effects of a High Fat Diet on Endometrial Tumour Biology
Organism Rattus norvegicus
Experiment type Expression profiling by high throughput sequencing
Summary We sought to validate the BDII/Han rat model as a model for diet-induced obesity in endometrial cancer (EC) and determine if transcriptomic changes induced by a high fat diet (HFD) in an EC rat model can be used to identify novel biomarkers in human EC. Nineteen BDII/Han rats were included. Group A (n = 7) were given ad lib access to a normal calorie, normal chow diet (NCD) while Group B (n = 12) were given ad lib access to a calorie rich HFD for 15 months. RNAseq was performed on endometrial tumours from both groups. The top-ranking differentially expressed genes (DEGs) were examined in the human EC using The Cancer Genome Atlas (TCGA) to assess if the BDII/Han rat model is an appropriate model for human obesity-induced carcinogenesis. Weight gain in HFD rats was double the weight gain of NCD rats (50 g vs. 25 g). The incidence of cancer was similar in both groups (4/7-57% vs. 4/12-33%; p = 0.37). All tumours were equivalent to a Stage 1A, Grade 2 human endometrioid carcinoma. A total of 368 DEGs were identified between the tumours in the HFD group compared to the NCD group. We identified two upstream regulators of the DEGs, mir-33 and Brd4, and a pathway analysis identified downstream enrichment of the colorectal cancer metastasis and ovarian cancer metastasis pathways. Top-ranking DEGs included Tex14, A2M, Hmgcs2, Adamts5, Pdk4, Crabp2, Capn12, Npw, Idi1 and Gpt. A2M expression was decreased in HFD tumours. Consistent with these findings, we found a significant negative correlation between A2M mRNA expression levels and BMI in the TCGA cohort (Spearman's Rho = -0.263, p < 0.001). A2M expression was associated with improved overall survival (HR = 0.45, 95% CI 0.23-0.9, p = 0.024). Crabp2 expression was increased in HFD tumours. In human EC, CRABP2 expression was associated with reduced overall survival (HR = 3.554, 95% CI 1.875-6.753, p < 0.001). Diet-induced obesity can alter EC transcriptomic profiles. The BDII/Han rat model is a suitable model of diet-induced obesity in endometrial cancer and can be used to identify clinically relevant biomarkers in human EC.
 
Overall design n=67 samples, from n=24 animals, from tumour (n=32) and normal tissue (n=35), representing n=4 conditions based on Diet (high fat - HFD; normal chow - NC) and Intervention in HFD (n=3; No intervention - NO; Liraglutide - LIR; Diet Restriction - RES).
Web link https://github.com/brucemoran/rdl_RNAseq
 
Contributor(s) Wilkinson M, Brennan D, LeRoux C, Moran B
Citation(s) 32927694
Submission date Mar 31, 2020
Last update date Feb 07, 2021
Contact name Bruce Moran
E-mail(s) bruce.moran@gmail.com
Organization name St. Vincent's University Hospital
Department Dept. of Pathology
Lab Molecular Lab
Street address Nutley Lane, Dublin 4
City Dublin
ZIP/Postal code D4
Country Ireland
 
Platforms (1)
GPL20084 Illumina NextSeq 500 (Rattus norvegicus)
Samples (67)
GSM4447250 S1_Individual1_TissueNormal_DietNC_InterventionNO_BatchF18FTSEUHT1008_RATetsE
GSM4447251 S2_Individual1_TissueTumour_DietNC_InterventionNO_BatchF18FTSEUHT1008_RATetsE
GSM4447252 S3_Individual1_TissueTumour_DietNC_InterventionNO_BatchF18FTSEUHT1008_RATetsE
Relations
BioProject PRJNA622308
SRA SRP254808

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Supplementary file Size Download File type/resource
GSE147864_rdl_RNAseq.sleuthObject.Rdata.gz 107.9 Mb (ftp)(http) RDATA
GSE147864_rdl_RNAseq.sleuthObject.obs_raw.tsv.gz 41.6 Mb (ftp)(http) TSV
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Raw data are available in SRA
Processed data are available on Series record
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